ERβ Impedes Prostate Cancer EMT by Destabilizing HIF-1α and Inhibiting VEGF-Mediated Snail Nuclear Localization: Implications for Gleason Grading

被引：331

作者：

Mak, Paul ^{[1
]}

Leav, Irwin ^{[1
]}

Pursell, Bryan ^{[1
]}

Bae, Donggoo ^{[1
]}

Yang, Xiaofang ^{[1
]}

Taglienti, Cherie A. ^{[1
]}

Gouvin, Lindsey M. ^{[1
]}

Sharma, Vishva M. ^{[1
]}

Mercurio, Arthur M. ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA

来源：

CANCER CELL | 2010年 / 17卷 / 04期

关键词：

ESTROGEN-RECEPTOR-BETA; ENDOTHELIAL GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; E-CADHERIN EXPRESSION; BREAST-CANCER; CARCINOMA-CELLS; TUMOR-CELLS; TRANSCRIPTIONAL REPRESSOR; RECENT TRENDS; ALPHA;

D O I：

10.1016/j.ccr.2010.02.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

High Gleason grade prostate carcinomas are aggressive, poorly differentiated tumors that exhibit diminished estrogen receptor beta (ER beta) expression. We report that a key function of ER beta and its specific ligand 5 alpha-androstane-3 beta,17 beta-diol (3 beta-adiol) is to maintain an epithelial phenotype and repress mesenchymal characteristics in prostate carcinoma. Stimuli (TGF-beta and hypoxia) that induce an epithelial-mesenchymal transition (EMT) diminish ER beta expression, and loss of ER beta is sufficient to promote an EMT. The mechanism involves ER beta-mediated destabilization of HIF-1 alpha and transcriptional repression of VEGF-A. The VEGF-A receptor neuropilin-1 drives the EMT by promoting Snaill nuclear localization. Importantly, this mechanism is manifested in high Gleason grade cancers, which exhibit significantly more HIF-1 alpha and VEGF expression, and Snail1 nuclear localization compared to low Gleason grade cancers.

引用

页码：319 / 332

页数：14

共 73 条

[1] Inducible FGFR-1 activation leads to irreversible prostate adenocarcinoma and an epithelial-to-mesenchymal transition [J].

Acevedo, Victor D. ;

Gangula, Rama D. ;

Freeman, Kevin W. ;

Li, Rile ;

Zhang, Youngyou ;

Wang, Fen ;

Ayala, Gustavo E. ;

Peterson, Leif E. ;

Ittmann, Michael ;

Spencer, David M. .

CANCER CELL, 2007, 12 (06) :559-571

[2] Mortality Results from a Randomized Prostate-Cancer Screening Trial [J].

Andriole, Gerald L. ;

Grubb, Robert L., III ;

Buys, Saundra S. ;

Chia, David ;

Church, Timothy R. ;

Fouad, Mona N. ;

Gelmann, Edward P. ;

Kvale, Paul A. ;

Reding, Douglas J. ;

Weissfeld, Joel L. ;

Yokochi, Lance A. ;

Crawford, E. David ;

O'Brien, Barbara ;

Clapp, Jonathan D. ;

Rathmell, Joshua M. ;

Riley, Thomas L. ;

Hayes, Richard B. ;

Kramer, Barnett S. ;

Izmirlian, Grant ;

Miller, Anthony B. ;

Pinsky, Paul F. ;

Prorok, Philip C. ;

Gohagan, John K. ;

Berg, Christine D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (13) :1310-1319

[3] Glycogen synthase kinase-3 is an endogenous inhibitor of snail transcription: implications for the epithelial-mesenchymal transition [J].

Bachelder, RE ;

Yoon, SO ;

Franci, C ;

de Herreros, AG ;

Mercurio, AM .

JOURNAL OF CELL BIOLOGY, 2005, 168 (01) :29-33

[4]

Bachelder RE, 2001, CANCER RES, V61, P5736

[5] Metabolic stress induces the lysosomal degradation of neuropilin-1 but not neuropilin-2 [J].

Bae, Donggoo ;

Lu, Shaolei ;

Taglienti, Cherie A. ;

Mercurio, Arthur M. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (42) :28074-28080

[6] Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids [J].

Bates, RC ;

Goldsmith, JD ;

Bachelder, RE ;

Brown, C ;

Shibuya, M ;

Oettgen, P ;

Mercurio, AM .

CURRENT BIOLOGY, 2003, 13 (19) :1721-1727

[7] Correlation of Snail expression with histological grade and lymph node status in breast carcinomas [J].

Blanco, MJ ;

Moreno-Bueno, G ;

Sarrio, D ;

Locascio, A ;

Cano, A ;

Palacios, J ;

Nieto, MA .

ONCOGENE, 2002, 21 (20) :3241-3246

[8]

Brown JM, 1999, CANCER RES, V59, P5863

[9]

Buteau-Lozano H, 2002, CANCER RES, V62, P4977

[10] Neuropilin-1 Upholds Dedifferentiation and Propagation Phenotypes of Renal Cell Carcinoma Cells by Activating Akt and Sonic Hedgehog Axes [J].

Cao, Ying ;

Wang, Ling ;

Nandy, Debashis ;

Zhang, Ying ;

Basu, Ananda ;

Radisky, Derek ;

Mukhopadhyay, Debabrata .

CANCER RESEARCH, 2008, 68 (21) :8667-8672

← 1 2 3 4 5 6 7 8 →