Ezrin mediates c-Myc actions in prostate cancer cell invasion

被引：59

作者：

Chuan, Y-C ^{[1
,2
]}

Iglesias-Gato, D. ^{[2
]}

Fernandez-Perez, L. ^{[3
,4
]}

Cedazo-Minguez, A. ^{[5
]}

Pang, S-T ^{[6
]}

Norstedt, G. ^{[2
]}

Pousette, A. ^{[7
]}

Flores-Morales, A.

机构：

[1] Univ Copenhagen, Fac Hlth Sci, Ctr Prot Res, Novo Nordisk Fdn, DK-2200 Copenhagen, Denmark

[2] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[3] Univ Las Palmas GC, Dept Clin Sci, Las Palmas Gran Canaria, Spain

[4] Canary Inst Canc Res, Las Palmas Gran Canaria, Spain

[5] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden

[6] Chang Gung Univ, Chang Gung Mem Hosp, Coll Med, Dept Surg,Div Urol, Tao Yuan, Taiwan

[7] Karolinska Inst, Androl Ctr, Stockholm, Sweden

来源：

ONCOGENE | 2010年 / 29卷 / 10期

基金：

瑞典研究理事会;

关键词：

ezrin; c-Myc; metastasis; cell invasion; androgen; ANDROGEN RECEPTOR; GENE-EXPRESSION; AKT ACTIVITY; IN-VIVO; PROGRESSION; ACTIVATION; SUPPRESSOR; PATHWAYS; GROWTH; PTEN;

D O I：

10.1038/onc.2009.442

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the regulation of prostate cancer cell invasion. We found that c-Myc induces cell invasion and anchorage-independent growth by regulating ezrin protein expression in the presence of androgens. The activity of the ezrin promoter is controlled by androgens through c-Myc, which binds to a phylogenetically conserved E-Box located in the proximal promoter region. Besides, we also show that ezrin is an important regulator of c-Myc protein levels. These effects are achieved through androgen-induced changes in ezrin phosphorylation, which results in the regulation of downstream signals. These downstream signals involve the modulation of Akt and GSK-3 beta activity resulting in increased c-Myc protein synthesis and inhibition of its degradation. In summary, we have shown a key role for ezrin as a mediator of c-Myc-induced tumorigenesis in prostate cancer cells. Oncogene (2010) 29, 1531-1542; doi:10.1038/onc.2009.442; published online 14 December 2009

引用

页码：1531 / 1542

页数：12