TRPM3 and miR-204 Establish a Regulatory Circuit that Controls Oncogenic Autophagy in Clear Cell Renal Cell Carcinoma

被引：217

作者：

Hall, Daniel P. ^{[1
]}

Cost, Nicholas G. ^{[1
,5
]}

Hegde, Shailaja ^{[1
]}

Kellner, Emily ^{[1
]}

Mikhaylova, Olga ^{[1
]}

Stratton, Yiwen ^{[1
]}

Ehmer, Birgit ^{[1
]}

Abplanalp, William A. ^{[1
]}

Pandey, Raghav ^{[1
]}

Biesiada, Jacek ^{[4
]}

Harteneck, Christian ^{[6
,7
]}

Plas, David R. ^{[1
]}

Meller, Jarek ^{[3
,4
,8
]}

Czyzyk-Krzeska, Maria F. ^{[1
,2
]}

机构：

[1] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45267 USA

[2] VA Res Serv, Dept Vet Affairs, Cincinnati, OH 45220 USA

[3] Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA

[4] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA

[5] Cincinnati Childrens Hosp Med Ctr, Div Pediat Urol, Cincinnati, OH 45229 USA

[6] Univ Tubingen, Eberhard Karls Univ Hosp & Clin, Inst Expt & Clin Pharmacol & Toxicol, Dept Pharmacol & Expt Therapy, D-72074 Tubingen, Germany

[7] Univ Tubingen, Interfac Ctr Pharmacogen & Drug Res, D-72074 Tubingen, Germany

[8] Nicolas Copernicus Univ, Dept Informat, PL-87100 Torun, Poland

来源：

CANCER CELL | 2014年 / 26卷 / 05期

关键词：

HORMONE-RELATED PROTEIN; KINASE KINASE-BETA; RNA-POLYMERASE-II; DIFFERENTIAL EXPRESSION; GROWTH-FACTOR; TUMOR-GROWTH; CAVEOLIN-1; CHANNELS; SURVIVAL; PATHWAY;

D O I：

10.1016/j.ccell.2014.09.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Autophagy promotes tumor growth by generating nutrients from the degradation of intracellular structures. Here we establish, using shRNAs, a dominant-negative mutant, and a pharmacologic inhibitor, mefenamic acid (MFA), that the Transient Receptor Potential Melastatin 3 (TRPM3) channel promotes the growth of clear cell renal cell carcinoma (ccRCC) and stimulates MAP1LC3A (LC3A) and MAP1LC3B (LC3B) autophagy. Increased expression of TRPM3 in RCC leads to Ca2+ influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca2+ and Zn2+ fluxes inhibit miR-214, which directly targets LC3A and LC3B. The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 directly through miR-204 and indirectly through another miR-204 target, Caveolin 1 (CAV1).

引用

页码：738 / 753

页数：16

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