Title: YAP modifies cancer cell sensitivity to EGFR and survivin inhibitors and is negatively regulated by the non-receptor type protein tyrosine phosphatase 14.
Authors: Huang, J-M; Nagatomo, I; Suzuki, E; Mizuno, T; Kumagai, T; Berezov, A; Zhang, H; Karlan, B; Greene, M I; Wang, Q
Published In Oncogene, (2013 Apr 25)
Abstract: 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.
PubMed ID: 22689061
MeSH Terms: Adaptor Proteins, Signal Transducing/chemistry; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism*; Amino Acid Motifs; Animals; Antineoplastic Agents/pharmacology*; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cisplatin/pharmacology; Gene Knockdown Techniques; Genes, Reporter; HEK293 Cells; Humans; Inhibitor of Apoptosis Proteins/antagonists & inhibitors*; Inhibitor of Apoptosis Proteins/metabolism; Luciferases, Renilla/biosynthesis; Luciferases, Renilla/genetics; Mice; NIH 3T3 Cells; Peptide Fragments/chemistry; Phosphoproteins/chemistry; Phosphoproteins/genetics; Phosphoproteins/metabolism*; Protein Binding; Protein Interaction Domains and Motifs; Protein Interaction Mapping; Protein Tyrosine Phosphatases, Non-Receptor/chemistry; Protein Tyrosine Phosphatases, Non-Receptor/metabolism*; Quinazolines/pharmacology*; RNA, Small Interfering/genetics; Receptor, Epidermal Growth Factor/antagonists & inhibitors*; Receptor, Epidermal Growth Factor/metabolism; Transcription Factors/metabolism; Transcriptional Activation