JWA regulates melanoma metastasis by integrin αVβ3 signaling

被引：68

作者：

Bai, J. ^{[1
,2
]}

Zhang, J. ^{[1
,3
]}

Wu, J. ^{[1
]}

Shen, L. ^{[1
]}

Zeng, J. ^{[1
]}

Ding, J. ^{[1
]}

Wu, Y. ^{[1
]}

Gong, Z. ^{[1
]}

Li, A. ^{[1
]}

Xu, S. ^{[1
]}

Zhou, J. ^{[1
]}

Li, G. ^{[2
]}

机构：

[1] Nanjing Med Univ, Sch Publ Hlth, Dept Mol Cell Biol & Toxicol, Ctr Canc, Nanjing 210029, Peoples R China

[2] Univ British Columbia, Dept Dermatol & Skin Sci, Jack Bell Res Ctr, Vancouver Coastal Hlth Res Inst, Vancouver, BC V5Z 1M9, Canada

[3] Nantong Canc Hosp, Dept Pathol, Nantong, Jiangsu Prov, Peoples R China

来源：

ONCOGENE | 2010年 / 29卷 / 08期

基金：

加拿大健康研究院; 中国国家自然科学基金;

关键词：

JWA; melanoma; metastasis; integrin; V BETA 3; CANCER-CELLS; ALPHA-V-BETA-3; INTEGRIN; VITRONECTIN RECEPTOR; MALIGNANT-MELANOMA; ARSENIC TRIOXIDE; PC12; CELLS; EXPRESSION; PROTEIN; ADHESION;

D O I：

10.1038/onc.2009.408

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：

JWA, a newly identified novel microtubule-associated protein (MAP), was recently demonstrated to be indispensable for the rearrangement of actin cytoskeleton and activation of MAPK cascades induced by arsenic trioxide (As2O3) and phorbol ester (PMA). JWA depletion blocked the inhibitory effect of As2O3 on HeLa cell migration, but enhanced cell migration after PMA treatment. As cancer cell migration is a hallmark of tumor metastasis and the functional role of JWA in cancer metastasis is not understood, here we show that JWA has an important role in melanoma metastasis. Our data demonstrated that JWA knockdown increased the adhesion and invasion abilities of melanoma cells. Furthermore, JWA knockdown in B16-F10 and A375 melanoma cells significantly promoted the formation and growth of metastatic colonies in vivo. Moreover, in the tumor biopsies from human melanoma patients, JWA expression was significantly decreased in malignant melanoma compared with normal nevi. In addition, we found that JWA knockdown could intensify tumor integrin alpha(V)beta(3) signaling by regulating nuclear factor Sp1. These findings suggest that JWA suppresses melanoma metastasis and may serve a potential therapeutic target for human melanoma. Oncogene (2010) 29, 1227-1237; doi: 10.1038/onc.2009.408; published online 30 November 2009

引用

页码：1227 / 1237

页数：11

共 42 条

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