Macroautophagy modulates cellular response to proteasome inhibitors in cancer therapy

被引：46

作者：

Wu, William K. K. ^{[1
,2
]}

Sakamoto, Kathleen M. ^{[3
]}

Milani, Manuela ^{[4
]}

Aldana-Masankgay, Grace ^{[3
]}

Fan, Daiming ^{[5
,6
]}

Wu, Kaichun ^{[5
,6
]}

Lee, Chung W. ^{[1
,2
]}

Cho, Chi H. ^{[1
,2
]}

Yu, Jun ^{[1
,2
]}

Sung, Joseph J. Y. ^{[1
,2
]}

机构：

[1] Chinese Univ Hong Kong, LKS Inst Hlth, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China

[2] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China

[3] Univ Calif Los Angeles, David Geffen Sch Med,Mattel Childrens Hosp UCLA, Gwynne Hazen Cherry Mem Labs,Calif Nanosyst Inst, Jonsson Comprehens Canc Ctr,Mol Biol Inst,Div Hem, Los Angeles, CA 90095 USA

[4] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Growth Factor Grp,Canc Res UK,Mol Oncol Labs, Oxford OX3 9DU, England

[5] Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian 710032, Peoples R China

[6] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian 710032, Peoples R China

来源：

DRUG RESISTANCE UPDATES | 2010年 / 13卷 / 03期

关键词：

HDAC6; IRE1-JNK; ATF4; mTOR; LC3; Aggresome; Bortezomib; ENDOPLASMIC-RETICULUM STRESS; PROTEIN-DEGRADATION; DEATH PATHWAYS; PHASE-II; KAPPA-B; AUTOPHAGY; BORTEZOMIB; APOPTOSIS; CELLS; RESISTANCE;

D O I：

10.1016/j.drup.2010.04.003

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Macroautophagy and the ubiquitin-proteasome system are two complementary pathways for protein degradation. The former degrades long-lived proteins and damaged organelles while the later degrades short-lived proteins. Recent findings indicate that suppression of the ubiquitin-proteasome system by proteasome inhibitors induces macroautophagy through multiple pathways, including) accumulation of ubiquitinated proteins and activation of HDAC6; (2) activation of the IRE1-JNK pathway; (3) proteasomal stabilization of ATF4; (4) inhibition of mTOR complex 1 signaling; (5) reduced proteasomal degradation of LC3. Induction of macroautophagy attenuates the antitumor effect of proteasome inhibitors in various types of cancer. These findings suggest that inhibition of macroautophagy may represent a novel strategy to enhance cellular sensitivity to proteasome inhibition. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：87 / 92

页数：6

共 83 条

[1] Autophagy delays apoptotic death in breast cancer cells following DNA damage [J].