Tumor cells can evade dependence on autophagy through adaptation.
Tumor cells can evade dependence on autophagy through adaptation.
复制标题
DOI：
10.1016/j.bbrc.2012.07.090
复制
发表时间：
2012-08-31
影响因子：
3.1
通讯作者：
Yin, Xiao-Ming
中科院分区：
文献类型：
--
作者：
Ding, Wen-Xing;Chen, Xi;Yin, Xiao-Ming
The autophagy-lysosome and the proteasome constitute the two major intracellular degradation systems. Suppression of the proteasome promotes autophagy for compensation and simultaneous inhibition of autophagy can selectively increase apoptosis in transformed cells, but not in untransformed or normal cells. Transformed cells are thus more dependent on autophagy for survival. However, it is unclear whether long-term autophagy inhibition/insufficiency would affect such dependency. To address this question, we transformed wild-type and autophagy-deficient cells lacking a key autophagy-related gene Atg5 with activated Ras. We found that such transformation did not make the autophagy-deficient tumor cells more susceptible to proteasome inhibitors than the wild type tumor cells, although the transformed cells were in general more sensitive to proteasome inhibition. We then compared the effect of acute versus constitutive knock-down of a key autophagy initiating molecule, Beclin 1, in an already transformed cancer cell line. In a wild-type U251 glioblastoma cell line (autophagy intact), increased sensitivity to proteasome inhibition was induced immediately after the knock-down of Beclin 1 expression with a specific siRNA (acute autophagy deficiency). On the other hand, when the tumor cell line was selected over a long period to achieve constitutive knock-down of Beclin 1, its sensitivity to proteasome inhibitors was no higher than that of the wild-type tumor cells. These results suggest that long-term autophagy deficiency either before or after oncogenic transformation can render the tumor cell survival independent of the autophagic activity, and the response to chemotherapy is no longer affected by the manipulation of the autophagy status.
登录
查看更多内容
影响因子：
10.5
作者：
Wei, Huijun;Wei, Shuang;Guan, Jun-Lin
通讯作者：
Guan, Jun-Lin
自噬参与致癌K-RAS诱导的恶性细胞转化。
DOI：
10.1074/jbc.m110.138958
发表时间：
2011-04-15
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kim MJ;Woo SJ;Yoon CH;Lee JS;An S;Choi YH;Hwang SG;Yoon G;Lee SJ
通讯作者：
Lee SJ
影响因子：
5.7
作者：
Ding WX;Ni HM;Gao W;Chen X;Kang JH;Stolz DB;Liu J;Yin XM
通讯作者：
Yin XM
影响因子：
10.5
作者：
Mathew, Robin;Kongara, Sameera;White, Eileen
通讯作者：
White, Eileen
影响因子：
10.5
作者：
Guo, Jessie Yanxiang;Chen, Hsin-Yi;White, Eileen
通讯作者：
White, Eileen