Kinome-wide siRNA screening identifies molecular targets mediating the sensitivity of pancreatic cancer cells to Aurora kinase inhibitors.
Kinome-wide siRNA screening identifies molecular targets mediating the sensitivity of pancreatic cancer cells to Aurora kinase inhibitors.
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DOI：
10.1016/j.bcp.2011.11.005
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发表时间：
2012-02-15
影响因子：
5.8
通讯作者：
Han, Haiyong
中科院分区：
文献类型：
--
作者：
Xie, Lifang;Kassner, Michelle;Munoz, Ruben M.;Que, Qiang Q.;Kiefer, Jeff;Zhao, Yu;Mousses, Spyro;Yin, Hongwei H.;Von Hoff, Daniel D.;Han, Haiyong
Aurora kinases are a family of mitotic kinases that play important roles in the tumorigenesis of a variety of cancers including pancreatic cancer. A number of Aurora kinase inhibitors (AKIs) are currently being tested in preclinical and clinical settings as anti-cancer therapies. However, the antitumor activity of AKIs in clinical trials has been modest. In order to improve the antitumor activity of AKIs in pancreatic cancer, we utilized a kinome focused RNAi screen to identify genes that, when silenced, would sensitize pancreatic cancer cells to AKI treatment. A total of 17 kinase genes were identified and confirmed as positive hits. One of the hits was the platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), which has been shown to be overexpressed in pancreatic cancer cells and tumor tissues. Imatinib, a PDGFR inhibitor, significantly enhanced the anti-proliferative effect of ZM447439, an Aurora B specific inhibitor, and PHA-739358, a pan-Aurora kinase inhibitor. Further studies showed that imatinib augmented the induction of G2/M cell cycle arrest and apoptosis by PHA-739358. These findings indicate that PDGFRA is a potential mediator of AKI sensitivity in pancreatic cancer cells.
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影响因子：
8
作者：
Kanda, A;Kawai, H;Tatsuka, M
通讯作者：
Tatsuka, M
影响因子：
5.7
作者：
Carpinelli, Patrizia;Ceruti, Roberta;Moll, Jurgen
通讯作者：
Moll, Jurgen
DOI：
10.1158/1078-0432.ccr-10-2214
发表时间：
2011-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Diep CH;Munoz RM;Choudhary A;Von Hoff DD;Han H
通讯作者：
Han H
影响因子：
4.8
作者：
Benten, Daniel;Keller, Gunhild;Brummendorf, Tim H.
通讯作者：
Brummendorf, Tim H.
影响因子：
3.6
作者：
Chen S;Auletta T;Dovirak O;Hutter C;Kuntz K;El-ftesi S;Kendall J;Han H;Von Hoff DD;Ashfaq R;Maitra A;Iacobuzio-Donahue CA;Hruban RH;Lucito R
通讯作者：
Lucito R