Journal
ONCOGENE
Volume 32, Issue 17, Pages 2220-2229Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.231
Keywords
ovarian cancer; YAP; PTPN14; EGFR; survivin; erlotinib
Funding
- Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute of the Cedars-Sinai Medical Center
- Donna and Jesse Garber Award for Cancer Research
- National Cancer Institute [R01CA089481, R01 CA055306]
- Breast Cancer Research Foundation
- Abramson Family Cancer Research Institute at the University of Pennsylvania
- Abramson Cancer Center [P30CA016520]
- CEET [ES013508-04]
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The Yes-associated protein (YAP) is a transcriptional factor involved in tissue development and tumorigenesis. Although YAP has been recognized as a key element of the Hippo signaling pathway, the mechanisms that regulate YAP activities remain to be fully characterized. In this study, we demonstrate that the non-receptor type protein tyrosine phosphatase 14 (PTPN14) functions as a negative regulator of YAP. We show that YAP forms a protein complex with PTPN14 through the WW domains of YAP and the PPXY motifs of PTPN14. In addition, PTPN14 inhibits YAP-mediated transcriptional activities. Knockdown of YAP sensitizes cancer cells to various anti-cancer agents, such as cisplatin, the EGFR tyrosine kinase inhibitor erlotinib and the small-molecule antagonist of survivin, S12. YAP-targeted modalities may be used in combination with other cancer drugs to achieve maximal therapeutic effects. Oncogene (2013) 32, 2220-2229; doi:10.1038/onc.2012.231; published online 11 June 2012
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