ERBB3 knockdown induces cell cycle arrest and activation of Bak and Bax-dependent apoptosis in colon cancer cells
- 주제(키워드) ERBB3 targeting , Cell cycle arrest , Apoptosis , Bak , Bax
- 등재 SCIE, SCOPUS
- 발행기관 IMPACT JOURNALS LLC
- 발행년도 2014
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000114490
- 본문언어 영어
- Published As http://dx.doi.org/10.18632/oncotarget.2094
초록/요약
ERBB3 is an emerging target for cancer therapy among the EGFR family. Contrary to resistance against EGFR and ERBB2 targeting, the genetic inhibition of ERBB3 results in anti-tumorigenic in HCT116 colon cancer cells harboring constitutively active KRAS and PIK3CA mutations. Still, the anti-tumorigenic molecular mechanism has not been defined. We demonstrated in this study that ERBB3 knockdown resulted in cell cycle arrest and activation of Bak and Bax-dependent apoptosis. Apoptosis was irrelevant to the majority of BH3-only pro-apoptotic proteins and correlated with the transcriptional upregulation of Bak and p53-dependent Bax translocation. Treatment with LY294002, a PI3K inhibitor, resulted in cell cycle arrest without apoptosis and a concomitant down-regulation of cap-dependent translation by the suppression of the PI3K/AKT/mTOR pathway. However, the inhibition of cap-dependent translation by ERBB3 knockdown occurred without altering the PI3K/AKT/mTOR pathway. In addition, ERBB3 knockdown-induced cell cycle arrest was observed in most colon cancer cells but was accompanied by apoptosis in p53 wild-type cells. These results indicate that ERBB3 is a potential target for EGFR-and ERBB2-resistant colon cancer therapy.
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