Yes-associated protein (YAP) functions as a tumor suppressor in breast

被引：283

作者：

Yuan, M.

Tomlinson, V.

Lara, R. ^{[2
]}

Holliday, D. ^{[3
]}

Chelala, C. ^{[4
]}

Harada, T. ^{[4
]}

Gangeswaran, R. ^{[4
]}

Manson-Bishop, C. ^{[5
]}

Smith, P. ^{[6
]}

Danovi, S. A.

Pardo, O. ^{[2
]}

Crook, T. ^{[6
]}

Mein, C. A. ^{[5
]}

Lemoine, N. R. ^{[4
]}

Jones, L. J. ^{[3
]}

Basu, S. ^{[1
]}

机构：

[1] Queen Mary Univ London, Barts & London Sch Med & Dent, Inst Canc, Ctr Mol Oncol,Cell Survival Signalling Lab, London EC1M 6BQ, England

[2] Univ London Imperial Coll Sci Technol & Med, Cellular Regulatory Networks Lab, London W12 ONN, England

[3] Inst Canc Res, Ctr Tumour Biol, Breast Pathol Grp, London EC1M 6BQ, England

[4] Inst Canc Res, Ctr Mol Oncol, Mol Pathol Lab, London EC1M 6BQ, England

[5] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Genome Ctr, London EC1M 6BQ, England

[6] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

来源：

CELL DEATH AND DIFFERENTIATION | 2008年 / 15卷 / 11期

关键词：

Yes-associated protein; breast cancer; loss of heterozygosity; tumor suppressor; anoikis; invasion;

D O I：

10.1038/cdd.2008.108

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：

Yes-associated protein (YAP) has been shown to positively regulate p53 family members and to be negatively regulated by the AKT proto-oncogene product in promoting apoptosis. On the basis of this function and its location at 11q22.2, a site of frequent loss of heterozygosity (LOH) in breast cancer, we investigated whether YAP is a tumor suppressor in breast. Examination of tumors by immunohistochemistry demonstrated significant loss of YAP protein. LOH analysis revealed that protein loss correlates with specific deletion of the YAP gene locus. Functionally, short hairpin RNA knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, inhibited the response to taxol and enhanced tumor growth in nude mice. This is the first report indicating YAP as a tumor suppressor, revealing its decreased expression in breast cancer as well as demonstrating the functional implications of YAP loss in several aspects of cancer signaling.

引用

页码：1752 / 1759

页数：8

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