期刊
CELL DEATH AND DIFFERENTIATION
卷 15, 期 11, 页码 1752-1759出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2008.108
关键词
Yes-associated protein; breast cancer; loss of heterozygosity; tumor suppressor; anoikis; invasion
资金
- Cancer Research UK
- The Research Advisory Board of St. Bartholomew's and The Royal London Charitable Foundation
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.
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