The extracellular matrix protein EMILIN1 silences the RAS-ERK pathway via α4β1 integrin and decreases tumor cell growth
Identifieur interne : 000035 ( Pmc/Checkpoint ); précédent : 000034; suivant : 000036The extracellular matrix protein EMILIN1 silences the RAS-ERK pathway via α4β1 integrin and decreases tumor cell growth
Auteurs : Teresa Maria Elisa Modica [Italie] ; Orlando Maiorani [Italie] ; Giulio Sartori [Italie] ; Eliana Pivetta [Italie] ; Roberto Doliana [Italie] ; Alessandra Capuano [Italie] ; Alfonso Colombatti [Italie] ; Paola Spessotto [Italie]Source :
- Oncotarget [ 1949-2553 ] ; 2017.
Abstract
The extracellular matrix plays a fundamental role in physiological and pathological proliferation. It exerts its function through a signal cascade starting from the integrins that take direct contact with matrix constituents most of which behave as pro-proliferative clues. On the contrary, EMILIN1, a glycoprotein interacting with the α4β1 integrin through its gC1q domain, plays a paradigmatic anti-proliferative role. Here, we demonstrate that the EMILIN1-α4 interaction de-activates the MAPK pathway through HRas. Epithelial cells expressing endogenous α4 integrin and persistently plated on gC1q inhibited pERK1/2 increasing HRasGTP and especially the HRasGTP ubiquitinated form (HRasGTP-Ub). The drug salirasib reversed this effect. In addition, only the gC1q-ligated α4 integrin chain co-immunoprecipitated the ubiquitinated HRas. Only epithelial cells transfected with the wild type form of the α4 integrin chain showed the EMILIN1/α4β1/HRas/pERK1/2 link, whereas cells transfected with a α4 integrin chain carrying a truncated cytoplasmic tail had no effect. In this study we unveiled the pathway activated by the gC1q domain of EMILIN1 through α4β1 integrin engagement and leading to the decrease of proliferation in an epithelial system.
Url:
DOI: 10.18632/oncotarget.15067
PubMed: 28177903
PubMed Central: 5432316
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>The extracellular matrix plays a fundamental role in physiological and pathological proliferation. It exerts its function through a signal cascade starting from the integrins that take direct contact with matrix constituents most of which behave as pro-proliferative clues. On the contrary, EMILIN1, a glycoprotein interacting with the α4β1 integrin through its gC1q domain, plays a paradigmatic anti-proliferative role. Here, we demonstrate that the EMILIN1-α4 interaction de-activates the MAPK pathway through HRas. Epithelial cells expressing endogenous α4 integrin and persistently plated on gC1q inhibited pERK1/2 increasing HRasGTP and especially the HRasGTP ubiquitinated form (HRasGTP-Ub). The drug salirasib reversed this effect. In addition, only the gC1q-ligated α4 integrin chain co-immunoprecipitated the ubiquitinated HRas. Only epithelial cells transfected with the wild type form of the α4 integrin chain showed the EMILIN1/α4β1/HRas/pERK1/2 link, whereas cells transfected with a α4 integrin chain carrying a truncated cytoplasmic tail had no effect. In this study we unveiled the pathway activated by the gC1q domain of EMILIN1 through α4β1 integrin engagement and leading to the decrease of proliferation in an epithelial system.</p>
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<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Moreno Layseca, P" uniqKey="Moreno Layseca P">P Moreno-Layseca</name>
</author>
<author><name sortKey="Streuli, Ch" uniqKey="Streuli C">CH Streuli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sjaastad, Md" uniqKey="Sjaastad M">MD Sjaastad</name>
</author>
<author><name sortKey="Lewis, Rs" uniqKey="Lewis R">RS Lewis</name>
</author>
<author><name sortKey="Nelson, Wj" uniqKey="Nelson W">WJ Nelson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Illario, M" uniqKey="Illario M">M Illario</name>
</author>
<author><name sortKey="Cavallo, Al" uniqKey="Cavallo A">AL Cavallo</name>
</author>
<author><name sortKey="Bayer, Ku" uniqKey="Bayer K">KU Bayer</name>
</author>
<author><name sortKey="Di, Mt" uniqKey="Di M">MT Di</name>
</author>
<author><name sortKey="Fenzi, G" uniqKey="Fenzi G">G Fenzi</name>
</author>
<author><name sortKey="Rossi, G" uniqKey="Rossi G">G Rossi</name>
</author>
<author><name sortKey="Vitale, M" uniqKey="Vitale M">M Vitale</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Downward, J" uniqKey="Downward J">J Downward</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barbacid, M" uniqKey="Barbacid M">M Barbacid</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Baker, Nm" uniqKey="Baker N">NM Baker</name>
</author>
<author><name sortKey="Der, Cj" uniqKey="Der C">CJ Der</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Oliff, A" uniqKey="Oliff A">A Oliff</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cox, Ad" uniqKey="Cox A">AD Cox</name>
</author>
<author><name sortKey="Der, Cj" uniqKey="Der C">CJ Der</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
<author><name sortKey="Bressan, Gm" uniqKey="Bressan G">GM Bressan</name>
</author>
<author><name sortKey="Castellani, I" uniqKey="Castellani I">I Castellani</name>
</author>
<author><name sortKey="Volpin, D" uniqKey="Volpin D">D Volpin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Doliana, R" uniqKey="Doliana R">R Doliana</name>
</author>
<author><name sortKey="Mongiat, M" uniqKey="Mongiat M">M Mongiat</name>
</author>
<author><name sortKey="Bucciotti, F" uniqKey="Bucciotti F">F Bucciotti</name>
</author>
<author><name sortKey="Giacomello, E" uniqKey="Giacomello E">E Giacomello</name>
</author>
<author><name sortKey="Deutzmann, R" uniqKey="Deutzmann R">R Deutzmann</name>
</author>
<author><name sortKey="Volpin, D" uniqKey="Volpin D">D Volpin</name>
</author>
<author><name sortKey="Bressan, Gm" uniqKey="Bressan G">GM Bressan</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
<author><name sortKey="Doliana, R" uniqKey="Doliana R">R Doliana</name>
</author>
<author><name sortKey="Bot, S" uniqKey="Bot S">S Bot</name>
</author>
<author><name sortKey="Canton, A" uniqKey="Canton A">A Canton</name>
</author>
<author><name sortKey="Mongiat, M" uniqKey="Mongiat M">M Mongiat</name>
</author>
<author><name sortKey="Mungiguerra, G" uniqKey="Mungiguerra G">G Mungiguerra</name>
</author>
<author><name sortKey="Paron Cilli, S" uniqKey="Paron Cilli S">S Paron-Cilli</name>
</author>
<author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mongiat, M" uniqKey="Mongiat M">M Mongiat</name>
</author>
<author><name sortKey="Mungiguerra, G" uniqKey="Mungiguerra G">G Mungiguerra</name>
</author>
<author><name sortKey="Bot, S" uniqKey="Bot S">S Bot</name>
</author>
<author><name sortKey="Mucignat, Mt" uniqKey="Mucignat M">MT Mucignat</name>
</author>
<author><name sortKey="Giacomello, E" uniqKey="Giacomello E">E Giacomello</name>
</author>
<author><name sortKey="Doliana, R" uniqKey="Doliana R">R Doliana</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
<author><name sortKey="Cervi, M" uniqKey="Cervi M">M Cervi</name>
</author>
<author><name sortKey="Mucignat, Mt" uniqKey="Mucignat M">MT Mucignat</name>
</author>
<author><name sortKey="Mungiguerra, G" uniqKey="Mungiguerra G">G Mungiguerra</name>
</author>
<author><name sortKey="Sartoretto, I" uniqKey="Sartoretto I">I Sartoretto</name>
</author>
<author><name sortKey="Doliana, R" uniqKey="Doliana R">R Doliana</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Danussi, C" uniqKey="Danussi C">C Danussi</name>
</author>
<author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
<author><name sortKey="Petrucco, A" uniqKey="Petrucco A">A Petrucco</name>
</author>
<author><name sortKey="Wassermann, B" uniqKey="Wassermann B">B Wassermann</name>
</author>
<author><name sortKey="Sabatelli, P" uniqKey="Sabatelli P">P Sabatelli</name>
</author>
<author><name sortKey="Montesi, M" uniqKey="Montesi M">M Montesi</name>
</author>
<author><name sortKey="Doliana, R" uniqKey="Doliana R">R Doliana</name>
</author>
<author><name sortKey="Bressan, Gm" uniqKey="Bressan G">GM Bressan</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Danussi, C" uniqKey="Danussi C">C Danussi</name>
</author>
<author><name sortKey="Del Bel, Bl" uniqKey="Del Bel B">BL Del Bel</name>
</author>
<author><name sortKey="Pivetta, E" uniqKey="Pivetta E">E Pivetta</name>
</author>
<author><name sortKey="Modica, Tm" uniqKey="Modica T">TM Modica</name>
</author>
<author><name sortKey="Muro, A" uniqKey="Muro A">A Muro</name>
</author>
<author><name sortKey="Wassermann, B" uniqKey="Wassermann B">B Wassermann</name>
</author>
<author><name sortKey="Doliana, R" uniqKey="Doliana R">R Doliana</name>
</author>
<author><name sortKey="Sabatelli, P" uniqKey="Sabatelli P">P Sabatelli</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
<author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pivetta, E" uniqKey="Pivetta E">E Pivetta</name>
</author>
<author><name sortKey="Wassermann, B" uniqKey="Wassermann B">B Wassermann</name>
</author>
<author><name sortKey="Del Bel, Bl" uniqKey="Del Bel B">BL Del Bel</name>
</author>
<author><name sortKey="Danussi, C" uniqKey="Danussi C">C Danussi</name>
</author>
<author><name sortKey="Modica, Tm" uniqKey="Modica T">TM Modica</name>
</author>
<author><name sortKey="Maiorani, O" uniqKey="Maiorani O">O Maiorani</name>
</author>
<author><name sortKey="Bosisio, G" uniqKey="Bosisio G">G Bosisio</name>
</author>
<author><name sortKey="Boccardo, F" uniqKey="Boccardo F">F Boccardo</name>
</author>
<author><name sortKey="Canzonieri, V" uniqKey="Canzonieri V">V Canzonieri</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
<author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Danussi, C" uniqKey="Danussi C">C Danussi</name>
</author>
<author><name sortKey="Petrucco, A" uniqKey="Petrucco A">A Petrucco</name>
</author>
<author><name sortKey="Wassermann, B" uniqKey="Wassermann B">B Wassermann</name>
</author>
<author><name sortKey="Pivetta, E" uniqKey="Pivetta E">E Pivetta</name>
</author>
<author><name sortKey="Modica, Tm" uniqKey="Modica T">TM Modica</name>
</author>
<author><name sortKey="Belluz, Lb" uniqKey="Belluz L">LB Belluz</name>
</author>
<author><name sortKey="Colombatti, A" uniqKey="Colombatti A">A Colombatti</name>
</author>
<author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walker, Jl" uniqKey="Walker J">JL Walker</name>
</author>
<author><name sortKey="Assoian, Rk" uniqKey="Assoian R">RK Assoian</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gilcrease, Mz" uniqKey="Gilcrease M">MZ Gilcrease</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Streuli, Ch" uniqKey="Streuli C">CH Streuli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schlaepfer, Dd" uniqKey="Schlaepfer D">DD Schlaepfer</name>
</author>
<author><name sortKey="Hanks, Sk" uniqKey="Hanks S">SK Hanks</name>
</author>
<author><name sortKey="Hunter, T" uniqKey="Hunter T">T Hunter</name>
</author>
<author><name sortKey="Van Der Geer, P" uniqKey="Van Der Geer P">P van der Geer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yonemoto, M" uniqKey="Yonemoto M">M Yonemoto</name>
</author>
<author><name sortKey="Satoh, T" uniqKey="Satoh T">T Satoh</name>
</author>
<author><name sortKey="Arakawa, H" uniqKey="Arakawa H">H Arakawa</name>
</author>
<author><name sortKey="Suzuki Takahashi, I" uniqKey="Suzuki Takahashi I">I Suzuki-Takahashi</name>
</author>
<author><name sortKey="Monden, Y" uniqKey="Monden Y">Y Monden</name>
</author>
<author><name sortKey="Kodera, T" uniqKey="Kodera T">T Kodera</name>
</author>
<author><name sortKey="Tanaka, K" uniqKey="Tanaka K">K Tanaka</name>
</author>
<author><name sortKey="Aoyama, T" uniqKey="Aoyama T">T Aoyama</name>
</author>
<author><name sortKey="Iwasawa, Y" uniqKey="Iwasawa Y">Y Iwasawa</name>
</author>
<author><name sortKey="Kamei, T" uniqKey="Kamei T">T Kamei</name>
</author>
<author><name sortKey="Nishimura, S" uniqKey="Nishimura S">S Nishimura</name>
</author>
<author><name sortKey="Tomimoto, K" uniqKey="Tomimoto K">K Tomimoto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kohl, Ne" uniqKey="Kohl N">NE Kohl</name>
</author>
<author><name sortKey="Mosser, Sd" uniqKey="Mosser S">SD Mosser</name>
</author>
<author><name sortKey="Desolms, Sj" uniqKey="Desolms S">SJ deSolms</name>
</author>
<author><name sortKey="Giuliani, Ea" uniqKey="Giuliani E">EA Giuliani</name>
</author>
<author><name sortKey="Pompliano, Dl" uniqKey="Pompliano D">DL Pompliano</name>
</author>
<author><name sortKey="Graham, Sl" uniqKey="Graham S">SL Graham</name>
</author>
<author><name sortKey="Smith, Rl" uniqKey="Smith R">RL Smith</name>
</author>
<author><name sortKey="Scolnick, Em" uniqKey="Scolnick E">EM Scolnick</name>
</author>
<author><name sortKey="Oliff, A" uniqKey="Oliff A">A Oliff</name>
</author>
<author><name sortKey="Gibbs, Jb" uniqKey="Gibbs J">JB Gibbs</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jura, N" uniqKey="Jura N">N Jura</name>
</author>
<author><name sortKey="Scotto Lavino, E" uniqKey="Scotto Lavino E">E Scotto-Lavino</name>
</author>
<author><name sortKey="Sobczyk, A" uniqKey="Sobczyk A">A Sobczyk</name>
</author>
<author><name sortKey="Bar Sagi, D" uniqKey="Bar Sagi D">D Bar-Sagi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gutierrez, L" uniqKey="Gutierrez L">L Gutierrez</name>
</author>
<author><name sortKey="Magee, Ai" uniqKey="Magee A">AI Magee</name>
</author>
<author><name sortKey="Marshall, Cj" uniqKey="Marshall C">CJ Marshall</name>
</author>
<author><name sortKey="Hancock, Jf" uniqKey="Hancock J">JF Hancock</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Berridge, Mj" uniqKey="Berridge M">MJ Berridge</name>
</author>
<author><name sortKey="Lipp, P" uniqKey="Lipp P">P Lipp</name>
</author>
<author><name sortKey="Bootman, Md" uniqKey="Bootman M">MD Bootman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roderick, Hl" uniqKey="Roderick H">HL Roderick</name>
</author>
<author><name sortKey="Cook, Sj" uniqKey="Cook S">SJ Cook</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dolmetsch, Re" uniqKey="Dolmetsch R">RE Dolmetsch</name>
</author>
<author><name sortKey="Lewis, Rs" uniqKey="Lewis R">RS Lewis</name>
</author>
<author><name sortKey="Goodnow, Cc" uniqKey="Goodnow C">CC Goodnow</name>
</author>
<author><name sortKey="Healy, Ji" uniqKey="Healy J">JI Healy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="He, F" uniqKey="He F">F He</name>
</author>
<author><name sortKey="Liu, W" uniqKey="Liu W">W Liu</name>
</author>
<author><name sortKey="Zheng, S" uniqKey="Zheng S">S Zheng</name>
</author>
<author><name sortKey="Zhou, L" uniqKey="Zhou L">L Zhou</name>
</author>
<author><name sortKey="Ye, B" uniqKey="Ye B">B Ye</name>
</author>
<author><name sortKey="Qi, Z" uniqKey="Qi Z">Z Qi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Neely, A" uniqKey="Neely A">A Neely</name>
</author>
<author><name sortKey="Hidalgo, P" uniqKey="Hidalgo P">P Hidalgo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morley, P" uniqKey="Morley P">P Morley</name>
</author>
<author><name sortKey="Whitfield, Jf" uniqKey="Whitfield J">JF Whitfield</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walker, Sa" uniqKey="Walker S">SA Walker</name>
</author>
<author><name sortKey="Cullen, Pj" uniqKey="Cullen P">PJ Cullen</name>
</author>
<author><name sortKey="Taylor, Ja" uniqKey="Taylor J">JA Taylor</name>
</author>
<author><name sortKey="Lockyer, Pj" uniqKey="Lockyer P">PJ Lockyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q Liu</name>
</author>
<author><name sortKey="Walker, Sa" uniqKey="Walker S">SA Walker</name>
</author>
<author><name sortKey="Gao, D" uniqKey="Gao D">D Gao</name>
</author>
<author><name sortKey="Taylor, Ja" uniqKey="Taylor J">JA Taylor</name>
</author>
<author><name sortKey="Dai, Yf" uniqKey="Dai Y">YF Dai</name>
</author>
<author><name sortKey="Arkell, Rs" uniqKey="Arkell R">RS Arkell</name>
</author>
<author><name sortKey="Bootman, Md" uniqKey="Bootman M">MD Bootman</name>
</author>
<author><name sortKey="Roderick, Hl" uniqKey="Roderick H">HL Roderick</name>
</author>
<author><name sortKey="Cullen, Pj" uniqKey="Cullen P">PJ Cullen</name>
</author>
<author><name sortKey="Lockyer, Pj" uniqKey="Lockyer P">PJ Lockyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Agell, N" uniqKey="Agell N">N Agell</name>
</author>
<author><name sortKey="Bachs, O" uniqKey="Bachs O">O Bachs</name>
</author>
<author><name sortKey="Rocamora, N" uniqKey="Rocamora N">N Rocamora</name>
</author>
<author><name sortKey="Villalonga, P" uniqKey="Villalonga P">P Villalonga</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cullen, Pj" uniqKey="Cullen P">PJ Cullen</name>
</author>
<author><name sortKey="Lockyer, Pj" uniqKey="Lockyer P">PJ Lockyer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xing, Jz" uniqKey="Xing J">JZ Xing</name>
</author>
<author><name sortKey="Zhu, L" uniqKey="Zhu L">L Zhu</name>
</author>
<author><name sortKey="Jackson, Ja" uniqKey="Jackson J">JA Jackson</name>
</author>
<author><name sortKey="Gabos, S" uniqKey="Gabos S">S Gabos</name>
</author>
<author><name sortKey="Sun, Xj" uniqKey="Sun X">XJ Sun</name>
</author>
<author><name sortKey="Wang, Xb" uniqKey="Wang X">XB Wang</name>
</author>
<author><name sortKey="Xu, X" uniqKey="Xu X">X Xu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Spessotto, P" uniqKey="Spessotto P">P Spessotto</name>
</author>
<author><name sortKey="Lacrima, K" uniqKey="Lacrima K">K Lacrima</name>
</author>
<author><name sortKey="Nicolosi, Pa" uniqKey="Nicolosi P">PA Nicolosi</name>
</author>
<author><name sortKey="Pivetta, E" uniqKey="Pivetta E">E Pivetta</name>
</author>
<author><name sortKey="Scapolan, M" uniqKey="Scapolan M">M Scapolan</name>
</author>
<author><name sortKey="Perris, R" uniqKey="Perris R">R Perris</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Oncotarget</journal-id>
<journal-id journal-id-type="iso-abbrev">Oncotarget</journal-id>
<journal-id journal-id-type="publisher-id">Oncotarget</journal-id>
<journal-id journal-id-type="publisher-id">ImpactJ</journal-id>
<journal-title-group><journal-title>Oncotarget</journal-title>
</journal-title-group>
<issn pub-type="epub">1949-2553</issn>
<publisher><publisher-name>Impact Journals LLC</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">28177903</article-id>
<article-id pub-id-type="pmc">5432316</article-id>
<article-id pub-id-type="publisher-id">15067</article-id>
<article-id pub-id-type="doi">10.18632/oncotarget.15067</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject>
</subj-group>
</article-categories>
<title-group><article-title>The extracellular matrix protein EMILIN1 silences the RAS-ERK pathway via α4β1 integrin and decreases tumor cell growth</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Modica</surname>
<given-names>Teresa Maria Elisa</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Maiorani</surname>
<given-names>Orlando</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sartori</surname>
<given-names>Giulio</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pivetta</surname>
<given-names>Eliana</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Doliana</surname>
<given-names>Roberto</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Capuano</surname>
<given-names>Alessandra</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Colombatti</surname>
<given-names>Alfonso</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Spessotto</surname>
<given-names>Paola</given-names>
</name>
<xref ref-type="aff" rid="A1"><sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="A1"><sup>1</sup>
Department of Translational Research, Experimental Oncology 2 Division, CRO Aviano, National Cancer Institute, Aviano, PN 33081, Italy</aff>
<author-notes><corresp id="cor1"><bold><italic>Correspondence to:</italic>
</bold>
<italic>Alfonso Colombatti,</italic>
<email>acolombatti@cro.it</email>
</corresp>
</author-notes>
<pub-date pub-type="collection"><day>18</day>
<month>4</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="epub"><day>3</day>
<month>2</month>
<year>2017</year>
</pub-date>
<volume>8</volume>
<issue>16</issue>
<fpage>27034</fpage>
<lpage>27046</lpage>
<history><date date-type="received"><day>26</day>
<month>10</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>9</day>
<month>1</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>Copyright: © 2017 Modica et al.</copyright-statement>
<copyright-year>2017</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0/"><license-p>This article is distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">Creative Commons Attribution License</ext-link>
(CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.</license-p>
</license>
</permissions>
<abstract><p>The extracellular matrix plays a fundamental role in physiological and pathological proliferation. It exerts its function through a signal cascade starting from the integrins that take direct contact with matrix constituents most of which behave as pro-proliferative clues. On the contrary, EMILIN1, a glycoprotein interacting with the α4β1 integrin through its gC1q domain, plays a paradigmatic anti-proliferative role. Here, we demonstrate that the EMILIN1-α4 interaction de-activates the MAPK pathway through HRas. Epithelial cells expressing endogenous α4 integrin and persistently plated on gC1q inhibited pERK1/2 increasing HRasGTP and especially the HRasGTP ubiquitinated form (HRasGTP-Ub). The drug salirasib reversed this effect. In addition, only the gC1q-ligated α4 integrin chain co-immunoprecipitated the ubiquitinated HRas. Only epithelial cells transfected with the wild type form of the α4 integrin chain showed the EMILIN1/α4β1/HRas/pERK1/2 link, whereas cells transfected with a α4 integrin chain carrying a truncated cytoplasmic tail had no effect. In this study we unveiled the pathway activated by the gC1q domain of EMILIN1 through α4β1 integrin engagement and leading to the decrease of proliferation in an epithelial system.</p>
</abstract>
<kwd-group><kwd>extracellular matrix</kwd>
<kwd>gC1q domain</kwd>
<kwd>α4β1 integrin</kwd>
<kwd>RAS-ERK pathway</kwd>
<kwd>proliferation</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Italie</li>
</country>
</list>
<tree><country name="Italie"><noRegion><name sortKey="Modica, Teresa Maria Elisa" sort="Modica, Teresa Maria Elisa" uniqKey="Modica T" first="Teresa Maria Elisa" last="Modica">Teresa Maria Elisa Modica</name>
</noRegion>
<name sortKey="Capuano, Alessandra" sort="Capuano, Alessandra" uniqKey="Capuano A" first="Alessandra" last="Capuano">Alessandra Capuano</name>
<name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name>
<name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name>
<name sortKey="Maiorani, Orlando" sort="Maiorani, Orlando" uniqKey="Maiorani O" first="Orlando" last="Maiorani">Orlando Maiorani</name>
<name sortKey="Pivetta, Eliana" sort="Pivetta, Eliana" uniqKey="Pivetta E" first="Eliana" last="Pivetta">Eliana Pivetta</name>
<name sortKey="Sartori, Giulio" sort="Sartori, Giulio" uniqKey="Sartori G" first="Giulio" last="Sartori">Giulio Sartori</name>
<name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name>
</country>
</tree>
</affiliations>
</record>
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