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Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition

Identifieur interne : 000470 ( Pmc/Curation ); précédent : 000469; suivant : 000471

Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition

Auteurs : Evdokia Michalopoulou [Royaume-Uni] ; Francesca R. Auciello [Royaume-Uni] ; Vinay Bulusu [Royaume-Uni] ; David Strachan [Royaume-Uni] ; Andrew D. Campbell [Royaume-Uni] ; Jacqueline Tait-Mulder [Royaume-Uni] ; Saadia A. Karim [Royaume-Uni] ; Jennifer P. Morton [Royaume-Uni] ; Owen J. Sansom [Royaume-Uni] ; Jurre J. Kamphorst [Royaume-Uni]

Source :

RBID : PMC:7043007

Abstract

Summary

Pancreatic ductal adenocarcinoma (PDAC) features a near-universal mutation in KRAS. Additionally, the tumor suppressor PTEN is lost in ∼10% of patients, and in mouse models, this dramatically accelerates tumor progression. While oncogenic KRAS and phosphatidylinositol 3-kinase (PI3K) cause divergent metabolic phenotypes individually, how they synergize to promote tumor metabolic alterations and dependencies remains unknown. We show that in KRAS-driven murine PDAC cells, loss of Pten strongly enhances both mTOR signaling and macropinocytosis. Protein scavenging alleviates sensitivity to mTOR inhibition by rescuing AKT phosphorylation at serine 473 and consequently cell proliferation. Combined inhibition of mTOR and lysosomal processing of internalized protein eliminates the macropinocytosis-mediated resistance. Our results indicate that mTORC2, rather than mTORC1, is an important regulator of protein scavenging and that protein-mediated resistance could explain the lack of effectiveness of mTOR inhibitors in certain genetic backgrounds. Concurrent inhibition of mTOR and protein scavenging might be a valuable therapeutic approach.


Url:
DOI: 10.1016/j.celrep.2020.01.080
PubMed: 32101748
PubMed Central: 7043007

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PMC:7043007

Le document en format XML

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<title>Summary</title>
<p>Pancreatic ductal adenocarcinoma (PDAC) features a near-universal mutation in
<italic>KRAS</italic>
. Additionally, the tumor suppressor
<italic>PTEN</italic>
is lost in ∼10% of patients, and in mouse models, this dramatically accelerates tumor progression. While oncogenic KRAS and phosphatidylinositol 3-kinase (PI3K) cause divergent metabolic phenotypes individually, how they synergize to promote tumor metabolic alterations and dependencies remains unknown. We show that in KRAS-driven murine PDAC cells, loss of
<italic>Pten</italic>
strongly enhances both mTOR signaling and macropinocytosis. Protein scavenging alleviates sensitivity to mTOR inhibition by rescuing AKT phosphorylation at serine 473 and consequently cell proliferation. Combined inhibition of mTOR and lysosomal processing of internalized protein eliminates the macropinocytosis-mediated resistance. Our results indicate that mTORC2, rather than mTORC1, is an important regulator of protein scavenging and that protein-mediated resistance could explain the lack of effectiveness of mTOR inhibitors in certain genetic backgrounds. Concurrent inhibition of mTOR and protein scavenging might be a valuable therapeutic approach.</p>
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<div1 type="bibliography">
<listBibl>
<biblStruct>
<analytic>
<author>
<name sortKey="Bar Sagi, D" uniqKey="Bar Sagi D">D. Bar-Sagi</name>
</author>
<author>
<name sortKey="Feramisco, J R" uniqKey="Feramisco J">J.R. Feramisco</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bloomfield, G" uniqKey="Bloomfield G">G. Bloomfield</name>
</author>
<author>
<name sortKey="Traynor, D" uniqKey="Traynor D">D. Traynor</name>
</author>
<author>
<name sortKey="Sander, S P" uniqKey="Sander S">S.P. Sander</name>
</author>
<author>
<name sortKey="Veltman, D M" uniqKey="Veltman D">D.M. Veltman</name>
</author>
<author>
<name sortKey="Pachebat, J A" uniqKey="Pachebat J">J.A. Pachebat</name>
</author>
<author>
<name sortKey="Kay, R R" uniqKey="Kay R">R.R. Kay</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Bryant, K L" uniqKey="Bryant K">K.L. Bryant</name>
</author>
<author>
<name sortKey="Mancias, J D" uniqKey="Mancias J">J.D. Mancias</name>
</author>
<author>
<name sortKey="Kimmelman, A C" uniqKey="Kimmelman A">A.C. Kimmelman</name>
</author>
<author>
<name sortKey="Der, C J" uniqKey="Der C">C.J. Der</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Chauhan, V P" uniqKey="Chauhan V">V.P. Chauhan</name>
</author>
<author>
<name sortKey="Boucher, Y" uniqKey="Boucher Y">Y. Boucher</name>
</author>
<author>
<name sortKey="Ferrone, C R" uniqKey="Ferrone C">C.R. Ferrone</name>
</author>
<author>
<name sortKey="Roberge, S" uniqKey="Roberge S">S. Roberge</name>
</author>
<author>
<name sortKey="Martin, J D" uniqKey="Martin J">J.D. Martin</name>
</author>
<author>
<name sortKey="Stylianopoulos, T" uniqKey="Stylianopoulos T">T. Stylianopoulos</name>
</author>
<author>
<name sortKey="Bardeesy, N" uniqKey="Bardeesy N">N. Bardeesy</name>
</author>
<author>
<name sortKey="Depinho, R A" uniqKey="Depinho R">R.A. DePinho</name>
</author>
<author>
<name sortKey="Padera, T P" uniqKey="Padera T">T.P. Padera</name>
</author>
<author>
<name sortKey="Munn, L L" uniqKey="Munn L">L.L. Munn</name>
</author>
<author>
<name sortKey="Jain, R K" uniqKey="Jain R">R.K. Jain</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Commisso, C" uniqKey="Commisso C">C. Commisso</name>
</author>
<author>
<name sortKey="Davidson, S M" uniqKey="Davidson S">S.M. Davidson</name>
</author>
<author>
<name sortKey="Soydaner Azeloglu, R G" uniqKey="Soydaner Azeloglu R">R.G. Soydaner-Azeloglu</name>
</author>
<author>
<name sortKey="Parker, S J" uniqKey="Parker S">S.J. Parker</name>
</author>
<author>
<name sortKey="Kamphorst, J J" uniqKey="Kamphorst J">J.J. Kamphorst</name>
</author>
<author>
<name sortKey="Hackett, S" uniqKey="Hackett S">S. Hackett</name>
</author>
<author>
<name sortKey="Grabocka, E" uniqKey="Grabocka E">E. Grabocka</name>
</author>
<author>
<name sortKey="Nofal, M" uniqKey="Nofal M">M. Nofal</name>
</author>
<author>
<name sortKey="Drebin, J A" uniqKey="Drebin J">J.A. Drebin</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Commisso, C" uniqKey="Commisso C">C. Commisso</name>
</author>
<author>
<name sortKey="Flinn, R J" uniqKey="Flinn R">R.J. Flinn</name>
</author>
<author>
<name sortKey="Bar Sagi, D" uniqKey="Bar Sagi D">D. Bar-Sagi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cybulski, N" uniqKey="Cybulski N">N. Cybulski</name>
</author>
<author>
<name sortKey="Hall, M N" uniqKey="Hall M">M.N. Hall</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Davidson, S M" uniqKey="Davidson S">S.M. Davidson</name>
</author>
<author>
<name sortKey="Jonas, O" uniqKey="Jonas O">O. Jonas</name>
</author>
<author>
<name sortKey="Keibler, M A" uniqKey="Keibler M">M.A. Keibler</name>
</author>
<author>
<name sortKey="Hou, H W" uniqKey="Hou H">H.W. Hou</name>
</author>
<author>
<name sortKey="Luengo, A" uniqKey="Luengo A">A. Luengo</name>
</author>
<author>
<name sortKey="Mayers, J R" uniqKey="Mayers J">J.R. Mayers</name>
</author>
<author>
<name sortKey="Wyckoff, J" uniqKey="Wyckoff J">J. Wyckoff</name>
</author>
<author>
<name sortKey="Del Rosario, A M" uniqKey="Del Rosario A">A.M. Del Rosario</name>
</author>
<author>
<name sortKey="Whitman, M" uniqKey="Whitman M">M. Whitman</name>
</author>
<author>
<name sortKey="Chin, C R" uniqKey="Chin C">C.R. Chin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Degenhardt, K" uniqKey="Degenhardt K">K. Degenhardt</name>
</author>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Degenhardt, K" uniqKey="Degenhardt K">K. Degenhardt</name>
</author>
<author>
<name sortKey="Chen, G" uniqKey="Chen G">G. Chen</name>
</author>
<author>
<name sortKey="Lindsten, T" uniqKey="Lindsten T">T. Lindsten</name>
</author>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Delgiorno, K E" uniqKey="Delgiorno K">K.E. DelGiorno</name>
</author>
<author>
<name sortKey="Carlson, M A" uniqKey="Carlson M">M.A. Carlson</name>
</author>
<author>
<name sortKey="Osgood, R" uniqKey="Osgood R">R. Osgood</name>
</author>
<author>
<name sortKey="Provenzano, P P" uniqKey="Provenzano P">P.P. Provenzano</name>
</author>
<author>
<name sortKey="Brockenbough, J S" uniqKey="Brockenbough J">J.S. Brockenbough</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
<author>
<name sortKey="Shepard, H M" uniqKey="Shepard H">H.M. Shepard</name>
</author>
<author>
<name sortKey="Frost, G I" uniqKey="Frost G">G.I. Frost</name>
</author>
<author>
<name sortKey="Potter, J D" uniqKey="Potter J">J.D. Potter</name>
</author>
<author>
<name sortKey="Hingorani, S R" uniqKey="Hingorani S">S.R. Hingorani</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Driscoll, D R" uniqKey="Driscoll D">D.R. Driscoll</name>
</author>
<author>
<name sortKey="Karim, S A" uniqKey="Karim S">S.A. Karim</name>
</author>
<author>
<name sortKey="Sano, M" uniqKey="Sano M">M. Sano</name>
</author>
<author>
<name sortKey="Gay, D M" uniqKey="Gay D">D.M. Gay</name>
</author>
<author>
<name sortKey="Jacob, W" uniqKey="Jacob W">W. Jacob</name>
</author>
<author>
<name sortKey="Yu, J" uniqKey="Yu J">J. Yu</name>
</author>
<author>
<name sortKey="Mizukami, Y" uniqKey="Mizukami Y">Y. Mizukami</name>
</author>
<author>
<name sortKey="Gopinathan, A" uniqKey="Gopinathan A">A. Gopinathan</name>
</author>
<author>
<name sortKey="Jodrell, D I" uniqKey="Jodrell D">D.I. Jodrell</name>
</author>
<author>
<name sortKey="Evans, T R" uniqKey="Evans T">T.R. Evans</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Dumontier, M" uniqKey="Dumontier M">M. Dumontier</name>
</author>
<author>
<name sortKey="Hocht, P" uniqKey="Hocht P">P. Höcht</name>
</author>
<author>
<name sortKey="Mintert, U" uniqKey="Mintert U">U. Mintert</name>
</author>
<author>
<name sortKey="Faix, J" uniqKey="Faix J">J. Faix</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ebner, M" uniqKey="Ebner M">M. Ebner</name>
</author>
<author>
<name sortKey="Sinkovics, B" uniqKey="Sinkovics B">B. Sinkovics</name>
</author>
<author>
<name sortKey="Szczygiel, M" uniqKey="Szczygiel M">M. Szczygieł</name>
</author>
<author>
<name sortKey="Ribeiro, D W" uniqKey="Ribeiro D">D.W. Ribeiro</name>
</author>
<author>
<name sortKey="Yudushkin, I" uniqKey="Yudushkin I">I. Yudushkin</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Elstrom, R L" uniqKey="Elstrom R">R.L. Elstrom</name>
</author>
<author>
<name sortKey="Bauer, D E" uniqKey="Bauer D">D.E. Bauer</name>
</author>
<author>
<name sortKey="Buzzai, M" uniqKey="Buzzai M">M. Buzzai</name>
</author>
<author>
<name sortKey="Karnauskas, R" uniqKey="Karnauskas R">R. Karnauskas</name>
</author>
<author>
<name sortKey="Harris, M H" uniqKey="Harris M">M.H. Harris</name>
</author>
<author>
<name sortKey="Plas, D R" uniqKey="Plas D">D.R. Plas</name>
</author>
<author>
<name sortKey="Zhuang, H" uniqKey="Zhuang H">H. Zhuang</name>
</author>
<author>
<name sortKey="Cinalli, R M" uniqKey="Cinalli R">R.M. Cinalli</name>
</author>
<author>
<name sortKey="Alavi, A" uniqKey="Alavi A">A. Alavi</name>
</author>
<author>
<name sortKey="Rudin, C M" uniqKey="Rudin C">C.M. Rudin</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Engelman, J A" uniqKey="Engelman J">J.A. Engelman</name>
</author>
<author>
<name sortKey="Luo, J" uniqKey="Luo J">J. Luo</name>
</author>
<author>
<name sortKey="Cantley, L C" uniqKey="Cantley L">L.C. Cantley</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Feng, J" uniqKey="Feng J">J. Feng</name>
</author>
<author>
<name sortKey="Park, J" uniqKey="Park J">J. Park</name>
</author>
<author>
<name sortKey="Cron, P" uniqKey="Cron P">P. Cron</name>
</author>
<author>
<name sortKey="Hess, D" uniqKey="Hess D">D. Hess</name>
</author>
<author>
<name sortKey="Hemmings, B A" uniqKey="Hemmings B">B.A. Hemmings</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Frost, L S" uniqKey="Frost L">L.S. Frost</name>
</author>
<author>
<name sortKey="Dhingra, A" uniqKey="Dhingra A">A. Dhingra</name>
</author>
<author>
<name sortKey="Reyes Reveles, J" uniqKey="Reyes Reveles J">J. Reyes-Reveles</name>
</author>
<author>
<name sortKey="Boesze Battaglia, K" uniqKey="Boesze Battaglia K">K. Boesze-Battaglia</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Garcia Carracedo, D" uniqKey="Garcia Carracedo D">D. Garcia-Carracedo</name>
</author>
<author>
<name sortKey="Turk, A T" uniqKey="Turk A">A.T. Turk</name>
</author>
<author>
<name sortKey="Fine, S A" uniqKey="Fine S">S.A. Fine</name>
</author>
<author>
<name sortKey="Akhavan, N" uniqKey="Akhavan N">N. Akhavan</name>
</author>
<author>
<name sortKey="Tweel, B C" uniqKey="Tweel B">B.C. Tweel</name>
</author>
<author>
<name sortKey="Parsons, R" uniqKey="Parsons R">R. Parsons</name>
</author>
<author>
<name sortKey="Chabot, J A" uniqKey="Chabot J">J.A. Chabot</name>
</author>
<author>
<name sortKey="Allendorf, J D" uniqKey="Allendorf J">J.D. Allendorf</name>
</author>
<author>
<name sortKey="Genkinger, J M" uniqKey="Genkinger J">J.M. Genkinger</name>
</author>
<author>
<name sortKey="Remotti, H E" uniqKey="Remotti H">H.E. Remotti</name>
</author>
<author>
<name sortKey="Su, G H" uniqKey="Su G">G.H. Su</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Georgescu, M M" uniqKey="Georgescu M">M.M. Georgescu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Guo, J Y" uniqKey="Guo J">J.Y. Guo</name>
</author>
<author>
<name sortKey="Chen, H Y" uniqKey="Chen H">H.Y. Chen</name>
</author>
<author>
<name sortKey="Mathew, R" uniqKey="Mathew R">R. Mathew</name>
</author>
<author>
<name sortKey="Fan, J" uniqKey="Fan J">J. Fan</name>
</author>
<author>
<name sortKey="Strohecker, A M" uniqKey="Strohecker A">A.M. Strohecker</name>
</author>
<author>
<name sortKey="Karsli Uzunbas, G" uniqKey="Karsli Uzunbas G">G. Karsli-Uzunbas</name>
</author>
<author>
<name sortKey="Kamphorst, J J" uniqKey="Kamphorst J">J.J. Kamphorst</name>
</author>
<author>
<name sortKey="Chen, G" uniqKey="Chen G">G. Chen</name>
</author>
<author>
<name sortKey="Lemons, J M" uniqKey="Lemons J">J.M. Lemons</name>
</author>
<author>
<name sortKey="Karantza, V" uniqKey="Karantza V">V. Karantza</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hill, R" uniqKey="Hill R">R. Hill</name>
</author>
<author>
<name sortKey="Calvopina, J H" uniqKey="Calvopina J">J.H. Calvopina</name>
</author>
<author>
<name sortKey="Kim, C" uniqKey="Kim C">C. Kim</name>
</author>
<author>
<name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name>
</author>
<author>
<name sortKey="Dawson, D W" uniqKey="Dawson D">D.W. Dawson</name>
</author>
<author>
<name sortKey="Donahue, T R" uniqKey="Donahue T">T.R. Donahue</name>
</author>
<author>
<name sortKey="Dry, S" uniqKey="Dry S">S. Dry</name>
</author>
<author>
<name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hingorani, S R" uniqKey="Hingorani S">S.R. Hingorani</name>
</author>
<author>
<name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name>
</author>
<author>
<name sortKey="Multani, A S" uniqKey="Multani A">A.S. Multani</name>
</author>
<author>
<name sortKey="Combs, C" uniqKey="Combs C">C. Combs</name>
</author>
<author>
<name sortKey="Deramaudt, T B" uniqKey="Deramaudt T">T.B. Deramaudt</name>
</author>
<author>
<name sortKey="Hruban, R H" uniqKey="Hruban R">R.H. Hruban</name>
</author>
<author>
<name sortKey="Rustgi, A K" uniqKey="Rustgi A">A.K. Rustgi</name>
</author>
<author>
<name sortKey="Chang, S" uniqKey="Chang S">S. Chang</name>
</author>
<author>
<name sortKey="Tuveson, D A" uniqKey="Tuveson D">D.A. Tuveson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Howell, J J" uniqKey="Howell J">J.J. Howell</name>
</author>
<author>
<name sortKey="Ricoult, S J" uniqKey="Ricoult S">S.J. Ricoult</name>
</author>
<author>
<name sortKey="Ben Sahra, I" uniqKey="Ben Sahra I">I. Ben-Sahra</name>
</author>
<author>
<name sortKey="Manning, B D" uniqKey="Manning B">B.D. Manning</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Hruban, R H" uniqKey="Hruban R">R.H. Hruban</name>
</author>
<author>
<name sortKey="Goggins, M" uniqKey="Goggins M">M. Goggins</name>
</author>
<author>
<name sortKey="Parsons, J" uniqKey="Parsons J">J. Parsons</name>
</author>
<author>
<name sortKey="Kern, S E" uniqKey="Kern S">S.E. Kern</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Javle, M M" uniqKey="Javle M">M.M. Javle</name>
</author>
<author>
<name sortKey="Shroff, R T" uniqKey="Shroff R">R.T. Shroff</name>
</author>
<author>
<name sortKey="Xiong, H" uniqKey="Xiong H">H. Xiong</name>
</author>
<author>
<name sortKey="Varadhachary, G A" uniqKey="Varadhachary G">G.A. Varadhachary</name>
</author>
<author>
<name sortKey="Fogelman, D" uniqKey="Fogelman D">D. Fogelman</name>
</author>
<author>
<name sortKey="Reddy, S A" uniqKey="Reddy S">S.A. Reddy</name>
</author>
<author>
<name sortKey="Davis, D" uniqKey="Davis D">D. Davis</name>
</author>
<author>
<name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name>
</author>
<author>
<name sortKey="Wolff, R A" uniqKey="Wolff R">R.A. Wolff</name>
</author>
<author>
<name sortKey="Abbruzzese, J L" uniqKey="Abbruzzese J">J.L. Abbruzzese</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kamphorst, J J" uniqKey="Kamphorst J">J.J. Kamphorst</name>
</author>
<author>
<name sortKey="Cross, J R" uniqKey="Cross J">J.R. Cross</name>
</author>
<author>
<name sortKey="Fan, J" uniqKey="Fan J">J. Fan</name>
</author>
<author>
<name sortKey="De Stanchina, E" uniqKey="De Stanchina E">E. de Stanchina</name>
</author>
<author>
<name sortKey="Mathew, R" uniqKey="Mathew R">R. Mathew</name>
</author>
<author>
<name sortKey="White, E P" uniqKey="White E">E.P. White</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
<author>
<name sortKey="Rabinowitz, J D" uniqKey="Rabinowitz J">J.D. Rabinowitz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kamphorst, J J" uniqKey="Kamphorst J">J.J. Kamphorst</name>
</author>
<author>
<name sortKey="Nofal, M" uniqKey="Nofal M">M. Nofal</name>
</author>
<author>
<name sortKey="Commisso, C" uniqKey="Commisso C">C. Commisso</name>
</author>
<author>
<name sortKey="Hackett, S R" uniqKey="Hackett S">S.R. Hackett</name>
</author>
<author>
<name sortKey="Lu, W" uniqKey="Lu W">W. Lu</name>
</author>
<author>
<name sortKey="Grabocka, E" uniqKey="Grabocka E">E. Grabocka</name>
</author>
<author>
<name sortKey="Vander Heiden, M G" uniqKey="Vander Heiden M">M.G. Vander Heiden</name>
</author>
<author>
<name sortKey="Miller, G" uniqKey="Miller G">G. Miller</name>
</author>
<author>
<name sortKey="Drebin, J A" uniqKey="Drebin J">J.A. Drebin</name>
</author>
<author>
<name sortKey="Bar Sagi, D" uniqKey="Bar Sagi D">D. Bar-Sagi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Karsli Uzunbas, G" uniqKey="Karsli Uzunbas G">G. Karsli-Uzunbas</name>
</author>
<author>
<name sortKey="Guo, J Y" uniqKey="Guo J">J.Y. Guo</name>
</author>
<author>
<name sortKey="Price, S" uniqKey="Price S">S. Price</name>
</author>
<author>
<name sortKey="Teng, X" uniqKey="Teng X">X. Teng</name>
</author>
<author>
<name sortKey="Laddha, S V" uniqKey="Laddha S">S.V. Laddha</name>
</author>
<author>
<name sortKey="Khor, S" uniqKey="Khor S">S. Khor</name>
</author>
<author>
<name sortKey="Kalaany, N Y" uniqKey="Kalaany N">N.Y. Kalaany</name>
</author>
<author>
<name sortKey="Jacks, T" uniqKey="Jacks T">T. Jacks</name>
</author>
<author>
<name sortKey="Chan, C S" uniqKey="Chan C">C.S. Chan</name>
</author>
<author>
<name sortKey="Rabinowitz, J D" uniqKey="Rabinowitz J">J.D. Rabinowitz</name>
</author>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kennedy, A L" uniqKey="Kennedy A">A.L. Kennedy</name>
</author>
<author>
<name sortKey="Morton, J P" uniqKey="Morton J">J.P. Morton</name>
</author>
<author>
<name sortKey="Manoharan, I" uniqKey="Manoharan I">I. Manoharan</name>
</author>
<author>
<name sortKey="Nelson, D M" uniqKey="Nelson D">D.M. Nelson</name>
</author>
<author>
<name sortKey="Jamieson, N B" uniqKey="Jamieson N">N.B. Jamieson</name>
</author>
<author>
<name sortKey="Pawlikowski, J S" uniqKey="Pawlikowski J">J.S. Pawlikowski</name>
</author>
<author>
<name sortKey="Mcbryan, T" uniqKey="Mcbryan T">T. McBryan</name>
</author>
<author>
<name sortKey="Doyle, B" uniqKey="Doyle B">B. Doyle</name>
</author>
<author>
<name sortKey="Mckay, C" uniqKey="Mckay C">C. McKay</name>
</author>
<author>
<name sortKey="Oien, K A" uniqKey="Oien K">K.A. Oien</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Kim, S M" uniqKey="Kim S">S.M. Kim</name>
</author>
<author>
<name sortKey="Nguyen, T T" uniqKey="Nguyen T">T.T. Nguyen</name>
</author>
<author>
<name sortKey="Ravi, A" uniqKey="Ravi A">A. Ravi</name>
</author>
<author>
<name sortKey="Kubiniok, P" uniqKey="Kubiniok P">P. Kubiniok</name>
</author>
<author>
<name sortKey="Finicle, B T" uniqKey="Finicle B">B.T. Finicle</name>
</author>
<author>
<name sortKey="Jayashankar, V" uniqKey="Jayashankar V">V. Jayashankar</name>
</author>
<author>
<name sortKey="Malacrida, L" uniqKey="Malacrida L">L. Malacrida</name>
</author>
<author>
<name sortKey="Hou, J" uniqKey="Hou J">J. Hou</name>
</author>
<author>
<name sortKey="Robertson, J" uniqKey="Robertson J">J. Robertson</name>
</author>
<author>
<name sortKey="Gao, D" uniqKey="Gao D">D. Gao</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Laplante, M" uniqKey="Laplante M">M. Laplante</name>
</author>
<author>
<name sortKey="Sabatini, D M" uniqKey="Sabatini D">D.M. Sabatini</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Lynch, C J" uniqKey="Lynch C">C.J. Lynch</name>
</author>
<author>
<name sortKey="Fox, H L" uniqKey="Fox H">H.L. Fox</name>
</author>
<author>
<name sortKey="Vary, T C" uniqKey="Vary T">T.C. Vary</name>
</author>
<author>
<name sortKey="Jefferson, L S" uniqKey="Jefferson L">L.S. Jefferson</name>
</author>
<author>
<name sortKey="Kimball, S R" uniqKey="Kimball S">S.R. Kimball</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mann, K M" uniqKey="Mann K">K.M. Mann</name>
</author>
<author>
<name sortKey="Ward, J M" uniqKey="Ward J">J.M. Ward</name>
</author>
<author>
<name sortKey="Yew, C C" uniqKey="Yew C">C.C. Yew</name>
</author>
<author>
<name sortKey="Kovochich, A" uniqKey="Kovochich A">A. Kovochich</name>
</author>
<author>
<name sortKey="Dawson, D W" uniqKey="Dawson D">D.W. Dawson</name>
</author>
<author>
<name sortKey="Black, M A" uniqKey="Black M">M.A. Black</name>
</author>
<author>
<name sortKey="Brett, B T" uniqKey="Brett B">B.T. Brett</name>
</author>
<author>
<name sortKey="Sheetz, T E" uniqKey="Sheetz T">T.E. Sheetz</name>
</author>
<author>
<name sortKey="Dupuy, A J" uniqKey="Dupuy A">A.J. Dupuy</name>
</author>
<author>
<name sortKey="Chang, D K" uniqKey="Chang D">D.K. Chang</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Manning, B D" uniqKey="Manning B">B.D. Manning</name>
</author>
<author>
<name sortKey="Toker, A" uniqKey="Toker A">A. Toker</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Mercer, J" uniqKey="Mercer J">J. Mercer</name>
</author>
<author>
<name sortKey="Helenius, A" uniqKey="Helenius A">A. Helenius</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Michalopoulou, E" uniqKey="Michalopoulou E">E. Michalopoulou</name>
</author>
<author>
<name sortKey="Bulusu, V" uniqKey="Bulusu V">V. Bulusu</name>
</author>
<author>
<name sortKey="Kamphorst, J J" uniqKey="Kamphorst J">J.J. Kamphorst</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Morran, D C" uniqKey="Morran D">D.C. Morran</name>
</author>
<author>
<name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name>
</author>
<author>
<name sortKey="Jamieson, N B" uniqKey="Jamieson N">N.B. Jamieson</name>
</author>
<author>
<name sortKey="Mrowinska, A" uniqKey="Mrowinska A">A. Mrowinska</name>
</author>
<author>
<name sortKey="Kalna, G" uniqKey="Kalna G">G. Kalna</name>
</author>
<author>
<name sortKey="Karim, S A" uniqKey="Karim S">S.A. Karim</name>
</author>
<author>
<name sortKey="Au, A Y" uniqKey="Au A">A.Y. Au</name>
</author>
<author>
<name sortKey="Scarlett, C J" uniqKey="Scarlett C">C.J. Scarlett</name>
</author>
<author>
<name sortKey="Chang, D K" uniqKey="Chang D">D.K. Chang</name>
</author>
<author>
<name sortKey="Pajak, M Z" uniqKey="Pajak M">M.Z. Pajak</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Nofal, M" uniqKey="Nofal M">M. Nofal</name>
</author>
<author>
<name sortKey="Zhang, K" uniqKey="Zhang K">K. Zhang</name>
</author>
<author>
<name sortKey="Han, S" uniqKey="Han S">S. Han</name>
</author>
<author>
<name sortKey="Rabinowitz, J D" uniqKey="Rabinowitz J">J.D. Rabinowitz</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Palm, W" uniqKey="Palm W">W. Palm</name>
</author>
<author>
<name sortKey="Park, Y" uniqKey="Park Y">Y. Park</name>
</author>
<author>
<name sortKey="Wright, K" uniqKey="Wright K">K. Wright</name>
</author>
<author>
<name sortKey="Pavlova, N N" uniqKey="Pavlova N">N.N. Pavlova</name>
</author>
<author>
<name sortKey="Tuveson, D A" uniqKey="Tuveson D">D.A. Tuveson</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="O Rey, J" uniqKey="O Rey J">J. O’Prey</name>
</author>
<author>
<name sortKey="Sakamaki, J" uniqKey="Sakamaki J">J. Sakamaki</name>
</author>
<author>
<name sortKey="Baudot, A D" uniqKey="Baudot A">A.D. Baudot</name>
</author>
<author>
<name sortKey="New, M" uniqKey="New M">M. New</name>
</author>
<author>
<name sortKey="Van Acker, T" uniqKey="Van Acker T">T. Van Acker</name>
</author>
<author>
<name sortKey="Tooze, S A" uniqKey="Tooze S">S.A. Tooze</name>
</author>
<author>
<name sortKey="Long, J S" uniqKey="Long J">J.S. Long</name>
</author>
<author>
<name sortKey="Ryan, K M" uniqKey="Ryan K">K.M. Ryan</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Palm, W" uniqKey="Palm W">W. Palm</name>
</author>
<author>
<name sortKey="Araki, J" uniqKey="Araki J">J. Araki</name>
</author>
<author>
<name sortKey="King, B" uniqKey="King B">B. King</name>
</author>
<author>
<name sortKey="Dematteo, R G" uniqKey="Dematteo R">R.G. DeMatteo</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Pavlova, N N" uniqKey="Pavlova N">N.N. Pavlova</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Perera, R M" uniqKey="Perera R">R.M. Perera</name>
</author>
<author>
<name sortKey="Stoykova, S" uniqKey="Stoykova S">S. Stoykova</name>
</author>
<author>
<name sortKey="Nicolay, B N" uniqKey="Nicolay B">B.N. Nicolay</name>
</author>
<author>
<name sortKey="Ross, K N" uniqKey="Ross K">K.N. Ross</name>
</author>
<author>
<name sortKey="Fitamant, J" uniqKey="Fitamant J">J. Fitamant</name>
</author>
<author>
<name sortKey="Boukhali, M" uniqKey="Boukhali M">M. Boukhali</name>
</author>
<author>
<name sortKey="Lengrand, J" uniqKey="Lengrand J">J. Lengrand</name>
</author>
<author>
<name sortKey="Deshpande, V" uniqKey="Deshpande V">V. Deshpande</name>
</author>
<author>
<name sortKey="Selig, M K" uniqKey="Selig M">M.K. Selig</name>
</author>
<author>
<name sortKey="Ferrone, C R" uniqKey="Ferrone C">C.R. Ferrone</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Perez Mancera, P A" uniqKey="Perez Mancera P">P.A. Pérez-Mancera</name>
</author>
<author>
<name sortKey="Rust, A G" uniqKey="Rust A">A.G. Rust</name>
</author>
<author>
<name sortKey="Van Der Weyden, L" uniqKey="Van Der Weyden L">L. van der Weyden</name>
</author>
<author>
<name sortKey="Kristiansen, G" uniqKey="Kristiansen G">G. Kristiansen</name>
</author>
<author>
<name sortKey="Li, A" uniqKey="Li A">A. Li</name>
</author>
<author>
<name sortKey="Sarver, A L" uniqKey="Sarver A">A.L. Sarver</name>
</author>
<author>
<name sortKey="Silverstein, K A" uniqKey="Silverstein K">K.A. Silverstein</name>
</author>
<author>
<name sortKey="Grutzmann, R" uniqKey="Grutzmann R">R. Grützmann</name>
</author>
<author>
<name sortKey="Aust, D" uniqKey="Aust D">D. Aust</name>
</author>
<author>
<name sortKey="Rummele, P" uniqKey="Rummele P">P. Rümmele</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Persad, S" uniqKey="Persad S">S. Persad</name>
</author>
<author>
<name sortKey="Attwell, S" uniqKey="Attwell S">S. Attwell</name>
</author>
<author>
<name sortKey="Gray, V" uniqKey="Gray V">V. Gray</name>
</author>
<author>
<name sortKey="Delcommenne, M" uniqKey="Delcommenne M">M. Delcommenne</name>
</author>
<author>
<name sortKey="Troussard, A" uniqKey="Troussard A">A. Troussard</name>
</author>
<author>
<name sortKey="Sanghera, J" uniqKey="Sanghera J">J. Sanghera</name>
</author>
<author>
<name sortKey="Dedhar, S" uniqKey="Dedhar S">S. Dedhar</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Provenzano, P P" uniqKey="Provenzano P">P.P. Provenzano</name>
</author>
<author>
<name sortKey="Cuevas, C" uniqKey="Cuevas C">C. Cuevas</name>
</author>
<author>
<name sortKey="Chang, A E" uniqKey="Chang A">A.E. Chang</name>
</author>
<author>
<name sortKey="Goel, V K" uniqKey="Goel V">V.K. Goel</name>
</author>
<author>
<name sortKey="Von Hoff, D D" uniqKey="Von Hoff D">D.D. Von Hoff</name>
</author>
<author>
<name sortKey="Hingorani, S R" uniqKey="Hingorani S">S.R. Hingorani</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rabinowitz, J D" uniqKey="Rabinowitz J">J.D. Rabinowitz</name>
</author>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rahib, L" uniqKey="Rahib L">L. Rahib</name>
</author>
<author>
<name sortKey="Smith, B D" uniqKey="Smith B">B.D. Smith</name>
</author>
<author>
<name sortKey="Aizenberg, R" uniqKey="Aizenberg R">R. Aizenberg</name>
</author>
<author>
<name sortKey="Rosenzweig, A B" uniqKey="Rosenzweig A">A.B. Rosenzweig</name>
</author>
<author>
<name sortKey="Fleshman, J M" uniqKey="Fleshman J">J.M. Fleshman</name>
</author>
<author>
<name sortKey="Matrisian, L M" uniqKey="Matrisian L">L.M. Matrisian</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Recouvreux, M V" uniqKey="Recouvreux M">M.V. Recouvreux</name>
</author>
<author>
<name sortKey="Commisso, C" uniqKey="Commisso C">C. Commisso</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Rosenfeldt, M T" uniqKey="Rosenfeldt M">M.T. Rosenfeldt</name>
</author>
<author>
<name sortKey="O Rey, J" uniqKey="O Rey J">J. O’Prey</name>
</author>
<author>
<name sortKey="Flossbach, L" uniqKey="Flossbach L">L. Flossbach</name>
</author>
<author>
<name sortKey="Nixon, C" uniqKey="Nixon C">C. Nixon</name>
</author>
<author>
<name sortKey="Morton, J P" uniqKey="Morton J">J.P. Morton</name>
</author>
<author>
<name sortKey="Sansom, O J" uniqKey="Sansom O">O.J. Sansom</name>
</author>
<author>
<name sortKey="Ryan, K M" uniqKey="Ryan K">K.M. Ryan</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sarbassov, D D" uniqKey="Sarbassov D">D.D. Sarbassov</name>
</author>
<author>
<name sortKey="Guertin, D A" uniqKey="Guertin D">D.A. Guertin</name>
</author>
<author>
<name sortKey="Ali, S M" uniqKey="Ali S">S.M. Ali</name>
</author>
<author>
<name sortKey="Sabatini, D M" uniqKey="Sabatini D">D.M. Sabatini</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Sarbassov, D D" uniqKey="Sarbassov D">D.D. Sarbassov</name>
</author>
<author>
<name sortKey="Ali, S M" uniqKey="Ali S">S.M. Ali</name>
</author>
<author>
<name sortKey="Sengupta, S" uniqKey="Sengupta S">S. Sengupta</name>
</author>
<author>
<name sortKey="Sheen, J H" uniqKey="Sheen J">J.H. Sheen</name>
</author>
<author>
<name sortKey="Hsu, P P" uniqKey="Hsu P">P.P. Hsu</name>
</author>
<author>
<name sortKey="Bagley, A F" uniqKey="Bagley A">A.F. Bagley</name>
</author>
<author>
<name sortKey="Markhard, A L" uniqKey="Markhard A">A.L. Markhard</name>
</author>
<author>
<name sortKey="Sabatini, D M" uniqKey="Sabatini D">D.M. Sabatini</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Scarpa, A" uniqKey="Scarpa A">A. Scarpa</name>
</author>
<author>
<name sortKey="Capelli, P" uniqKey="Capelli P">P. Capelli</name>
</author>
<author>
<name sortKey="Mukai, K" uniqKey="Mukai K">K. Mukai</name>
</author>
<author>
<name sortKey="Zamboni, G" uniqKey="Zamboni G">G. Zamboni</name>
</author>
<author>
<name sortKey="Oda, T" uniqKey="Oda T">T. Oda</name>
</author>
<author>
<name sortKey="Iacono, C" uniqKey="Iacono C">C. Iacono</name>
</author>
<author>
<name sortKey="Hirohashi, S" uniqKey="Hirohashi S">S. Hirohashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schneider, C A" uniqKey="Schneider C">C.A. Schneider</name>
</author>
<author>
<name sortKey="Rasband, W S" uniqKey="Rasband W">W.S. Rasband</name>
</author>
<author>
<name sortKey="Eliceiri, K W" uniqKey="Eliceiri K">K.W. Eliceiri</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schonleben, F" uniqKey="Schonleben F">F. Schönleben</name>
</author>
<author>
<name sortKey="Qiu, W" uniqKey="Qiu W">W. Qiu</name>
</author>
<author>
<name sortKey="Ciau, N T" uniqKey="Ciau N">N.T. Ciau</name>
</author>
<author>
<name sortKey="Ho, D J" uniqKey="Ho D">D.J. Ho</name>
</author>
<author>
<name sortKey="Li, X" uniqKey="Li X">X. Li</name>
</author>
<author>
<name sortKey="Allendorf, J D" uniqKey="Allendorf J">J.D. Allendorf</name>
</author>
<author>
<name sortKey="Remotti, H E" uniqKey="Remotti H">H.E. Remotti</name>
</author>
<author>
<name sortKey="Su, G H" uniqKey="Su G">G.H. Su</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Schreiber, K H" uniqKey="Schreiber K">K.H. Schreiber</name>
</author>
<author>
<name sortKey="Ortiz, D" uniqKey="Ortiz D">D. Ortiz</name>
</author>
<author>
<name sortKey="Academia, E C" uniqKey="Academia E">E.C. Academia</name>
</author>
<author>
<name sortKey="Anies, A C" uniqKey="Anies A">A.C. Anies</name>
</author>
<author>
<name sortKey="Liao, C Y" uniqKey="Liao C">C.Y. Liao</name>
</author>
<author>
<name sortKey="Kennedy, B K" uniqKey="Kennedy B">B.K. Kennedy</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Tong, X" uniqKey="Tong X">X. Tong</name>
</author>
<author>
<name sortKey="Zhao, F" uniqKey="Zhao F">F. Zhao</name>
</author>
<author>
<name sortKey="Thompson, C B" uniqKey="Thompson C">C.B. Thompson</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Tumanov, S" uniqKey="Tumanov S">S. Tumanov</name>
</author>
<author>
<name sortKey="Bulusu, V" uniqKey="Bulusu V">V. Bulusu</name>
</author>
<author>
<name sortKey="Kamphorst, J J" uniqKey="Kamphorst J">J.J. Kamphorst</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Vadlakonda, L" uniqKey="Vadlakonda L">L. Vadlakonda</name>
</author>
<author>
<name sortKey="Dash, A" uniqKey="Dash A">A. Dash</name>
</author>
<author>
<name sortKey="Pasupuleti, M" uniqKey="Pasupuleti M">M. Pasupuleti</name>
</author>
<author>
<name sortKey="Anil Kumar, K" uniqKey="Anil Kumar K">K. Anil Kumar</name>
</author>
<author>
<name sortKey="Reddanna, P" uniqKey="Reddanna P">P. Reddanna</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Veltman, D M" uniqKey="Veltman D">D.M. Veltman</name>
</author>
<author>
<name sortKey="Williams, T D" uniqKey="Williams T">T.D. Williams</name>
</author>
<author>
<name sortKey="Bloomfield, G" uniqKey="Bloomfield G">G. Bloomfield</name>
</author>
<author>
<name sortKey="Chen, B C" uniqKey="Chen B">B.C. Chen</name>
</author>
<author>
<name sortKey="Betzig, E" uniqKey="Betzig E">E. Betzig</name>
</author>
<author>
<name sortKey="Insall, R H" uniqKey="Insall R">R.H. Insall</name>
</author>
<author>
<name sortKey="Kay, R R" uniqKey="Kay R">R.R. Kay</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="White, E" uniqKey="White E">E. White</name>
</author>
<author>
<name sortKey="Dipaola, R S" uniqKey="Dipaola R">R.S. DiPaola</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wiza, C" uniqKey="Wiza C">C. Wiza</name>
</author>
<author>
<name sortKey="Nascimento, E B M" uniqKey="Nascimento E">E.B.M. Nascimento</name>
</author>
<author>
<name sortKey="Ouwens, D M" uniqKey="Ouwens D">D.M. Ouwens</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Wolpin, B M" uniqKey="Wolpin B">B.M. Wolpin</name>
</author>
<author>
<name sortKey="Hezel, A F" uniqKey="Hezel A">A.F. Hezel</name>
</author>
<author>
<name sortKey="Abrams, T" uniqKey="Abrams T">T. Abrams</name>
</author>
<author>
<name sortKey="Blaszkowsky, L S" uniqKey="Blaszkowsky L">L.S. Blaszkowsky</name>
</author>
<author>
<name sortKey="Meyerhardt, J A" uniqKey="Meyerhardt J">J.A. Meyerhardt</name>
</author>
<author>
<name sortKey="Chan, J A" uniqKey="Chan J">J.A. Chan</name>
</author>
<author>
<name sortKey="Enzinger, P C" uniqKey="Enzinger P">P.C. Enzinger</name>
</author>
<author>
<name sortKey="Allen, B" uniqKey="Allen B">B. Allen</name>
</author>
<author>
<name sortKey="Clark, J W" uniqKey="Clark J">J.W. Clark</name>
</author>
<author>
<name sortKey="Ryan, D P" uniqKey="Ryan D">D.P. Ryan</name>
</author>
<author>
<name sortKey="Fuchs, C S" uniqKey="Fuchs C">C.S. Fuchs</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Ying, H" uniqKey="Ying H">H. Ying</name>
</author>
<author>
<name sortKey="Elpek, K G" uniqKey="Elpek K">K.G. Elpek</name>
</author>
<author>
<name sortKey="Vinjamoori, A" uniqKey="Vinjamoori A">A. Vinjamoori</name>
</author>
<author>
<name sortKey="Zimmerman, S M" uniqKey="Zimmerman S">S.M. Zimmerman</name>
</author>
<author>
<name sortKey="Chu, G C" uniqKey="Chu G">G.C. Chu</name>
</author>
<author>
<name sortKey="Yan, H" uniqKey="Yan H">H. Yan</name>
</author>
<author>
<name sortKey="Fletcher Sananikone, E" uniqKey="Fletcher Sananikone E">E. Fletcher-Sananikone</name>
</author>
<author>
<name sortKey="Zhang, H" uniqKey="Zhang H">H. Zhang</name>
</author>
<author>
<name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name>
</author>
<author>
<name sortKey="Wang, W" uniqKey="Wang W">W. Wang</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Cell Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Cell Rep</journal-id>
<journal-title-group>
<journal-title>Cell Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2211-1247</issn>
<publisher>
<publisher-name>Cell Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">32101748</article-id>
<article-id pub-id-type="pmc">7043007</article-id>
<article-id pub-id-type="publisher-id">S2211-1247(20)30105-4</article-id>
<article-id pub-id-type="doi">10.1016/j.celrep.2020.01.080</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" id="au1">
<name>
<surname>Michalopoulou</surname>
<given-names>Evdokia</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au2">
<name>
<surname>Auciello</surname>
<given-names>Francesca R.</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au3">
<name>
<surname>Bulusu</surname>
<given-names>Vinay</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au4">
<name>
<surname>Strachan</surname>
<given-names>David</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="au5">
<name>
<surname>Campbell</surname>
<given-names>Andrew D.</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="au6">
<name>
<surname>Tait-Mulder</surname>
<given-names>Jacqueline</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au7">
<name>
<surname>Karim</surname>
<given-names>Saadia A.</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" id="au8">
<name>
<surname>Morton</surname>
<given-names>Jennifer P.</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au9">
<name>
<surname>Sansom</surname>
<given-names>Owen J.</given-names>
</name>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author" id="au10">
<name>
<surname>Kamphorst</surname>
<given-names>Jurre J.</given-names>
</name>
<email>jurre.kamphorst@glasgow.ac.uk</email>
<xref rid="aff1" ref-type="aff">1</xref>
<xref rid="aff2" ref-type="aff">2</xref>
<xref rid="fn1" ref-type="fn">3</xref>
<xref rid="fn2" ref-type="fn">4</xref>
<xref rid="cor1" ref-type="corresp"></xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK</aff>
<aff id="aff2">
<label>2</label>
Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, UK</aff>
<author-notes>
<corresp id="cor1">
<label></label>
Corresponding author
<email>jurre.kamphorst@glasgow.ac.uk</email>
</corresp>
<fn id="fn1">
<label>3</label>
<p id="ntpara0010">Present address: Rheos Medicines, 38 Sidney Street, Cambridge, MA 02139, USA</p>
</fn>
<fn id="fn2">
<label>4</label>
<p id="ntpara0015">Lead Contact</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release">
<day>25</day>
<month>2</month>
<year>2020</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection">
<day>25</day>
<month>2</month>
<year>2020</year>
</pub-date>
<pub-date pub-type="epub">
<day>25</day>
<month>2</month>
<year>2020</year>
</pub-date>
<volume>30</volume>
<issue>8</issue>
<fpage>2729</fpage>
<lpage>2742.e4</lpage>
<history>
<date date-type="received">
<day>19</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="rev-recd">
<day>14</day>
<month>10</month>
<year>2019</year>
</date>
<date date-type="accepted">
<day>21</day>
<month>1</month>
<year>2020</year>
</date>
</history>
<permissions>
<copyright-statement>© 2020 The Author(s)</copyright-statement>
<copyright-year>2020</copyright-year>
<license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p>
</license>
</permissions>
<abstract id="abs0010">
<title>Summary</title>
<p>Pancreatic ductal adenocarcinoma (PDAC) features a near-universal mutation in
<italic>KRAS</italic>
. Additionally, the tumor suppressor
<italic>PTEN</italic>
is lost in ∼10% of patients, and in mouse models, this dramatically accelerates tumor progression. While oncogenic KRAS and phosphatidylinositol 3-kinase (PI3K) cause divergent metabolic phenotypes individually, how they synergize to promote tumor metabolic alterations and dependencies remains unknown. We show that in KRAS-driven murine PDAC cells, loss of
<italic>Pten</italic>
strongly enhances both mTOR signaling and macropinocytosis. Protein scavenging alleviates sensitivity to mTOR inhibition by rescuing AKT phosphorylation at serine 473 and consequently cell proliferation. Combined inhibition of mTOR and lysosomal processing of internalized protein eliminates the macropinocytosis-mediated resistance. Our results indicate that mTORC2, rather than mTORC1, is an important regulator of protein scavenging and that protein-mediated resistance could explain the lack of effectiveness of mTOR inhibitors in certain genetic backgrounds. Concurrent inhibition of mTOR and protein scavenging might be a valuable therapeutic approach.</p>
</abstract>
<abstract abstract-type="graphical" id="abs0015">
<title>Graphical Abstract</title>
<fig id="undfig1" position="anchor">
<graphic xlink:href="fx1"></graphic>
</fig>
</abstract>
<abstract abstract-type="author-highlights" id="abs0020">
<title>Highlights</title>
<p>
<list list-type="simple" id="ulist0010">
<list-item id="u0010">
<label></label>
<p id="p0010">PTEN loss increases scavenging, conferring resistance to mTOR inhibition in PDAC</p>
</list-item>
<list-item id="u0015">
<label></label>
<p id="p0015">mTORC2 selectively regulates macropinocytosis independently of its kinase activity</p>
</list-item>
<list-item id="u0020">
<label></label>
<p id="p0020">Protein scavenging restores pAkt serine 473, leading to recovery of proliferation</p>
</list-item>
<list-item id="u0025">
<label></label>
<p id="p0025">Lysosomal blockade eliminates the protein-mediated resistance to mTOR inhibition</p>
</list-item>
</list>
</p>
</abstract>
<abstract abstract-type="teaser" id="abs0025">
<p>Michalopoulou et al. show that in pancreatic cancer cells with oncogenic KRAS and PTEN loss, scavenging of extracellular protein provides resistance against mTOR inhibition. Protein scavenging circumvents mTORC2 signaling by rescuing AKT phosphorylation. Additional treatment with AKT or lysosomal inhibitors strongly potentiates the effect of mTOR inhibitors.</p>
</abstract>
<kwd-group id="kwrds0010">
<title>Keywords</title>
<kwd>AKT</kwd>
<kwd>cancer metabolism</kwd>
<kwd>macropinocytosis</kwd>
<kwd>metabolic scavenging</kwd>
<kwd>mTORC2</kwd>
<kwd>pancreatic ductal adenocarcinoma</kwd>
</kwd-group>
</article-meta>
<notes>
<p id="misc0010">Published: February 25, 2020</p>
</notes>
</front>
</pmc>
</record>

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