A Derivate of Benzimidazole-Isoquinolinone Induces SKP2 Transcriptional Inhibition to Exert Anti-Tumor Activity in Glioblastoma Cells
Identifieur interne : 000B47 ( Main/Exploration ); précédent : 000B46; suivant : 000B48A Derivate of Benzimidazole-Isoquinolinone Induces SKP2 Transcriptional Inhibition to Exert Anti-Tumor Activity in Glioblastoma Cells
Auteurs : He-Ying Chen [République populaire de Chine] ; Liu-Jun He [République populaire de Chine] ; Shi-Qiang Li [République populaire de Chine] ; Ya-Jun Zhang [République populaire de Chine] ; Jiu-Hong Huang [République populaire de Chine] ; Hong-Xia Qin [République populaire de Chine] ; Juan-Li Wang [République populaire de Chine] ; Qian-Yin Li [République populaire de Chine] ; Dong-Lin Yang [République populaire de Chine]Source :
- Molecules [ 1420-3049 ] ; 2019.
Abstract
We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.
Url:
DOI: 10.3390/molecules24152722
PubMed: 31357480
PubMed Central: 6695871
Affiliations:
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Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Juan Li" sort="Wang, Juan Li" uniqKey="Wang J" first="Juan-Li" last="Wang">Juan-Li Wang</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 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xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016</wicri:regionArea><wicri:noRegion>Chongqing 400016</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molecules-24-02722">The Undergraduates Class of 2016 entry the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>The Undergraduates Class of 2016 entry the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016</wicri:regionArea><wicri:noRegion>Chongqing 400016</wicri:noRegion></affiliation></author><author><name sortKey="He, Liu Jun" sort="He, Liu Jun" uniqKey="He L" first="Liu-Jun" last="He">Liu-Jun He</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Li, Shi Qiang" sort="Li, Shi Qiang" uniqKey="Li S" first="Shi-Qiang" last="Li">Shi-Qiang Li</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Ya Jun" sort="Zhang, Ya Jun" uniqKey="Zhang Y" first="Ya-Jun" last="Zhang">Ya-Jun Zhang</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Jiu Hong" sort="Huang, Jiu Hong" uniqKey="Huang J" first="Jiu-Hong" last="Huang">Jiu-Hong Huang</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Qin, Hong Xia" sort="Qin, Hong Xia" uniqKey="Qin H" first="Hong-Xia" last="Qin">Hong-Xia Qin</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Juan Li" sort="Wang, Juan Li" uniqKey="Wang J" first="Juan-Li" last="Wang">Juan-Li Wang</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author><author><name sortKey="Li, Qian Yin" sort="Li, Qian Yin" uniqKey="Li Q" first="Qian-Yin" last="Li">Qian-Yin Li</name><affiliation wicri:level="1"><nlm:aff id="af1-molecules-24-02722">Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016</wicri:regionArea><wicri:noRegion>Chongqing 400016</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Dong Lin" sort="Yang, Dong Lin" uniqKey="Yang D" first="Dong-Lin" last="Yang">Dong-Lin Yang</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02722">Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160</wicri:regionArea><wicri:noRegion>Chongqing 402160</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecules</title><idno type="eISSN">1420-3049</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stupp, R" uniqKey="Stupp R">R. Stupp</name></author><author><name sortKey="Mason, W P" uniqKey="Mason W">W.P. Mason</name></author><author><name sortKey="Van Den Bent, M J" uniqKey="Van Den Bent M">M.J. Van Den Bent</name></author><author><name sortKey="Weller, M" uniqKey="Weller M">M. Weller</name></author><author><name sortKey="Fisher, B" uniqKey="Fisher B">B. Fisher</name></author><author><name sortKey="Taphoorn, M J" uniqKey="Taphoorn M">M.J. Taphoorn</name></author><author><name sortKey="Belanger, K" uniqKey="Belanger K">K. Belanger</name></author><author><name sortKey="Brandes, A A" uniqKey="Brandes A">A.A. Brandes</name></author><author><name sortKey="Marosi, C" uniqKey="Marosi C">C. Marosi</name></author><author><name sortKey="Bogdahn, U" uniqKey="Bogdahn U">U. Bogdahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wen, P Y" uniqKey="Wen P">P.Y. Wen</name></author><author><name sortKey="Kesari, S" uniqKey="Kesari S">S. Kesari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sathornsumetee, S" uniqKey="Sathornsumetee S">S. Sathornsumetee</name></author><author><name sortKey="Reardon, D A" uniqKey="Reardon D">D.A. Reardon</name></author><author><name sortKey="Desjardins, A" uniqKey="Desjardins A">A. Desjardins</name></author><author><name sortKey="Quinn, J A" uniqKey="Quinn J">J.A. Quinn</name></author><author><name sortKey="Vredenburgh, J J" uniqKey="Vredenburgh J">J.J. Vredenburgh</name></author><author><name sortKey="Rich, J N" uniqKey="Rich J">J.N. Rich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hueng, D Y" uniqKey="Hueng D">D.-Y. Hueng</name></author><author><name sortKey="Hsieh, C H" uniqKey="Hsieh C">C.-H. Hsieh</name></author><author><name sortKey="Cheng, Y C" uniqKey="Cheng Y">Y.-C. Cheng</name></author><author><name sortKey="Tsai, W C" uniqKey="Tsai W">W.-C. Tsai</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Fan, C" uniqKey="Fan C">C. Fan</name></author><author><name sortKey="Pu, L" uniqKey="Pu L">L. Pu</name></author><author><name sortKey="Wei, C" uniqKey="Wei C">C. Wei</name></author><author><name sortKey="Jin, H" uniqKey="Jin H">H. Jin</name></author><author><name sortKey="Teng, Y" uniqKey="Teng Y">Y. Teng</name></author><author><name sortKey="Zhao, M" uniqKey="Zhao M">M. Zhao</name></author><author><name sortKey="Yu, A C H" uniqKey="Yu A">A.C.H. Yu</name></author><author><name sortKey="Jiang, F" uniqKey="Jiang F">F. Jiang</name></author><author><name sortKey="Shu, J" uniqKey="Shu J">J. Shu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Y" uniqKey="Lee Y">Y. Lee</name></author><author><name sortKey="Lim, H S" uniqKey="Lim H">H.-S. Lim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z. Wang</name></author><author><name sortKey="Liu, P" uniqKey="Liu P">P. Liu</name></author><author><name sortKey="Inuzuka, H" uniqKey="Inuzuka H">H. Inuzuka</name></author><author><name sortKey="Wei, W" uniqKey="Wei W">W. Wei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, C H" uniqKey="Chan C">C.-H. Chan</name></author><author><name sortKey="Morrow, J K" uniqKey="Morrow J">J.K. Morrow</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S. Zhang</name></author><author><name sortKey="Lin, H K" uniqKey="Lin H">H.-K. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, I M" uniqKey="Chu I">I.M. Chu</name></author><author><name sortKey="Hengst, L" uniqKey="Hengst L">L. Hengst</name></author><author><name sortKey="Slingerland, J M" uniqKey="Slingerland J">J.M. Slingerland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reichert, M" uniqKey="Reichert M">M. Reichert</name></author><author><name sortKey="Saur, D" uniqKey="Saur D">D. Saur</name></author><author><name sortKey="Hamacher, R" uniqKey="Hamacher R">R. Hamacher</name></author><author><name sortKey="Schmid, R M" uniqKey="Schmid R">R.M. Schmid</name></author><author><name sortKey="Schneider, G" uniqKey="Schneider G">G. Schneider</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, Z" uniqKey="Lu Z">Z. Lu</name></author><author><name sortKey="Bauzon, F" uniqKey="Bauzon F">F. Bauzon</name></author><author><name sortKey="Fu, H" uniqKey="Fu H">H. Fu</name></author><author><name sortKey="Cui, J" uniqKey="Cui J">J. Cui</name></author><author><name sortKey="Zhao, H" uniqKey="Zhao H">H. Zhao</name></author><author><name sortKey="Nakayama, K" uniqKey="Nakayama K">K. Nakayama</name></author><author><name sortKey="Nakayama, K I" uniqKey="Nakayama K">K.I. Nakayama</name></author><author><name sortKey="Zhu, L" uniqKey="Zhu L">L. Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salon, C" uniqKey="Salon C">C. Salon</name></author><author><name sortKey="Merdzhanova, G" uniqKey="Merdzhanova G">G. Merdzhanova</name></author><author><name sortKey="Brambilla, C" uniqKey="Brambilla C">C. Brambilla</name></author><author><name sortKey="Brambilla, E" uniqKey="Brambilla E">E. Brambilla</name></author><author><name sortKey="Gazzeri, S" uniqKey="Gazzeri S">S. Gazzeri</name></author><author><name sortKey="Eymin, B" uniqKey="Eymin B">B. Eymin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, L J" uniqKey="He L">L.-J. He</name></author><author><name sortKey="Yang, D L" uniqKey="Yang D">D.-L. Yang</name></author><author><name sortKey="Li, S Q" uniqKey="Li S">S.-Q. Li</name></author><author><name sortKey="Zhang, Y J" uniqKey="Zhang Y">Y.-J. Zhang</name></author><author><name sortKey="Tang, Y" uniqKey="Tang Y">Y. Tang</name></author><author><name sortKey="Lei, J" uniqKey="Lei J">J. Lei</name></author><author><name sortKey="Frett, B" uniqKey="Frett B">B. Frett</name></author><author><name sortKey="Lin, H K" uniqKey="Lin H">H.-K. Lin</name></author><author><name sortKey="Li, H Y" uniqKey="Li H">H.-Y. Li</name></author><author><name sortKey="Chen, Z Z" uniqKey="Chen Z">Z.-Z. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kurland, J F" uniqKey="Kurland J">J.F. Kurland</name></author><author><name sortKey="Tansey, W P" uniqKey="Tansey W">W.P. Tansey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Li, R" uniqKey="Li R">R. Li</name></author><author><name sortKey="Yin, D" uniqKey="Yin D">D. Yin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jung, D" uniqKey="Jung D">D. Jung</name></author><author><name sortKey="Khurana, A" uniqKey="Khurana A">A. Khurana</name></author><author><name sortKey="Roy, D" uniqKey="Roy D">D. Roy</name></author><author><name sortKey="Kalogera, E" uniqKey="Kalogera E">E. Kalogera</name></author><author><name sortKey="Bakkum Gamez, J" uniqKey="Bakkum Gamez J">J. Bakkum-Gamez</name></author><author><name sortKey="Chien, J" uniqKey="Chien J">J. Chien</name></author><author><name sortKey="Shridhar, V" uniqKey="Shridhar V">V. Shridhar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, K" uniqKey="Liu K">K. Liu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Zhao, Q" uniqKey="Zhao Q">Q. Zhao</name></author><author><name sortKey="Zhao, Z" uniqKey="Zhao Z">Z. Zhao</name></author><author><name sortKey="Zhi, F" uniqKey="Zhi F">F. Zhi</name></author><author><name sortKey="Qin, Y" uniqKey="Qin Y">Y. Qin</name></author><author><name sortKey="Cui, J" uniqKey="Cui J">J. Cui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hao, Z" uniqKey="Hao Z">Z. Hao</name></author><author><name sortKey="Huang, S" uniqKey="Huang S">S. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, W" uniqKey="Lu W">W. Lu</name></author><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Xie, Y" uniqKey="Xie Y">Y. Xie</name></author><author><name sortKey="Adhiambo, C" uniqKey="Adhiambo C">C. Adhiambo</name></author><author><name sortKey="Yang, Q" uniqKey="Yang Q">Q. Yang</name></author><author><name sortKey="Ballard, B R" uniqKey="Ballard B">B.R. Ballard</name></author><author><name sortKey="Nakayama, K I" uniqKey="Nakayama K">K.I. Nakayama</name></author><author><name sortKey="Matusik, R J" uniqKey="Matusik R">R.J. Matusik</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wei, Z" uniqKey="Wei Z">Z. Wei</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author><author><name sortKey="Qiao, H" uniqKey="Qiao H">H. Qiao</name></author><author><name sortKey="Zhai, B" uniqKey="Zhai B">B. Zhai</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Zhang, Q" uniqKey="Zhang Q">Q. Zhang</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author><author><name sortKey="Jiang, H" uniqKey="Jiang H">H. Jiang</name></author><author><name sortKey="Sun, X" uniqKey="Sun X">X. Sun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, J" uniqKey="Luo J">J. Luo</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B. Wang</name></author><author><name sortKey="Li, Q" uniqKey="Li Q">Q. Li</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Lan, H" uniqKey="Lan H">H. Lan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, C" uniqKey="Yang C">C. Yang</name></author><author><name sortKey="Nan, H" uniqKey="Nan H">H. Nan</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J. Ma</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L. Jiang</name></author><author><name sortKey="Guo, Q" uniqKey="Guo Q">Q. Guo</name></author><author><name sortKey="Han, L" uniqKey="Han L">L. Han</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Nan, K" uniqKey="Nan K">K. Nan</name></author><author><name sortKey="Guo, H" uniqKey="Guo H">H. Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeh, C T" uniqKey="Yeh C">C.T. Yeh</name></author><author><name sortKey="So, M" uniqKey="So M">M. So</name></author><author><name sortKey="Ng, J" uniqKey="Ng J">J. Ng</name></author><author><name sortKey="Yang, H W" uniqKey="Yang H">H.W. Yang</name></author><author><name sortKey="Chang, M L" uniqKey="Chang M">M.L. Chang</name></author><author><name sortKey="Lai, M W" uniqKey="Lai M">M.W. Lai</name></author><author><name sortKey="Chen, T C" uniqKey="Chen T">T.C. Chen</name></author><author><name sortKey="Lin, C Y" uniqKey="Lin C">C.Y. Lin</name></author><author><name sortKey="Yeh, T S" uniqKey="Yeh T">T.S. Yeh</name></author><author><name sortKey="Lee, W C" uniqKey="Lee W">W.C. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="Cui, J" uniqKey="Cui J">J. Cui</name></author><author><name sortKey="Bauzon, F" uniqKey="Bauzon F">F. Bauzon</name></author><author><name sortKey="Zhu, L" uniqKey="Zhu L">L. Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beth, L" uniqKey="Beth L">L. Beth</name></author><author><name sortKey="Guido, K" uniqKey="Guido K">K. Guido</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawaguchi, Y" uniqKey="Kawaguchi Y">Y. Kawaguchi</name></author><author><name sortKey="Kovacs, J J" uniqKey="Kovacs J">J.J. Kovacs</name></author><author><name sortKey="Mclaurin, A" uniqKey="Mclaurin A">A. McLaurin</name></author><author><name sortKey="Vance, J M" uniqKey="Vance J">J.M. Vance</name></author><author><name sortKey="Ito, A" uniqKey="Ito A">A. Ito</name></author><author><name sortKey="Yao, T P" uniqKey="Yao T">T.-P. Yao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shin, H J R" uniqKey="Shin H">H.-J.R. Shin</name></author><author><name sortKey="Kim, H" uniqKey="Kim H">H. Kim</name></author><author><name sortKey="Oh, S" uniqKey="Oh S">S. Oh</name></author><author><name sortKey="Lee, J G" uniqKey="Lee J">J.-G. Lee</name></author><author><name sortKey="Kee, M" uniqKey="Kee M">M. Kee</name></author><author><name sortKey="Ko, H J" uniqKey="Ko H">H.-J. Ko</name></author><author><name sortKey="Kweon, M N" uniqKey="Kweon M">M.-N. Kweon</name></author><author><name sortKey="Won, K J" uniqKey="Won K">K.-J. Won</name></author><author><name sortKey="Baek, S H" uniqKey="Baek S">S.H. Baek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, J Y" uniqKey="Lee J">J.Y. Lee</name></author><author><name sortKey="Koga, H" uniqKey="Koga H">H. Koga</name></author><author><name sortKey="Kawaguchi, Y" uniqKey="Kawaguchi Y">Y. Kawaguchi</name></author><author><name sortKey="Tang, W" uniqKey="Tang W">W. Tang</name></author><author><name sortKey="Wong, E" uniqKey="Wong E">E. Wong</name></author><author><name sortKey="Gao, Y S" uniqKey="Gao Y">Y.S. Gao</name></author><author><name sortKey="Pandey, U B" uniqKey="Pandey U">U.B. Pandey</name></author><author><name sortKey="Kaushik, S" uniqKey="Kaushik S">S. Kaushik</name></author><author><name sortKey="Tresse, E" uniqKey="Tresse E">E. Tresse</name></author><author><name sortKey="Lu, J" uniqKey="Lu J">J. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mizushima, N" uniqKey="Mizushima N">N. Mizushima</name></author><author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T. Yoshimori</name></author><author><name sortKey="Levine, B" uniqKey="Levine B">B. Levine</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Chen, He Ying" sort="Chen, He Ying" uniqKey="Chen H" first="He-Ying" last="Chen">He-Ying Chen</name></noRegion><name sortKey="Chen, He Ying" sort="Chen, He Ying" uniqKey="Chen H" first="He-Ying" last="Chen">He-Ying Chen</name><name sortKey="Chen, He Ying" sort="Chen, He Ying" uniqKey="Chen H" first="He-Ying" last="Chen">He-Ying Chen</name><name sortKey="He, Liu Jun" sort="He, Liu Jun" uniqKey="He L" first="Liu-Jun" last="He">Liu-Jun He</name><name sortKey="Huang, Jiu Hong" sort="Huang, Jiu Hong" uniqKey="Huang J" first="Jiu-Hong" last="Huang">Jiu-Hong Huang</name><name sortKey="Li, Qian Yin" sort="Li, Qian Yin" uniqKey="Li Q" first="Qian-Yin" last="Li">Qian-Yin Li</name><name sortKey="Li, Shi Qiang" sort="Li, Shi Qiang" uniqKey="Li S" first="Shi-Qiang" last="Li">Shi-Qiang Li</name><name sortKey="Qin, Hong Xia" sort="Qin, Hong Xia" uniqKey="Qin H" first="Hong-Xia" last="Qin">Hong-Xia Qin</name><name sortKey="Wang, Juan Li" sort="Wang, Juan Li" uniqKey="Wang J" first="Juan-Li" last="Wang">Juan-Li Wang</name><name sortKey="Yang, Dong Lin" sort="Yang, Dong Lin" uniqKey="Yang D" first="Dong-Lin" last="Yang">Dong-Lin Yang</name><name sortKey="Zhang, Ya Jun" sort="Zhang, Ya Jun" uniqKey="Zhang Y" first="Ya-Jun" last="Zhang">Ya-Jun Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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