Abstract 1630: Critical role of Shp2 protein tyrosine phosphatase in tumorigenesis of carcinoma

Abstract Increasing evidence suggests that tumorigenic function requires coordinated action of both protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Certain PTPs, similar to PTKs, may play positive roles in the initiation and maintenance of human cancer. Shp2 is a non-receptor PTP encoded by the human PTPN11 gene. Gain-of-function Shp2 mutants have been linked to hematologic malignancies. While the role of Shp2 in carcinoma is less clear, Shp2 is a positive regulator of signaling by receptor tyrosine kinases such as EGFR, MET, and ALK that are involved in pathogenesis of carcinomas. To determine if Shp2 is required for tumor growth of carcinoma, we suppressed Shp2 expression and PTP activity using shRNAs and a PTP-inactive mutant in breast, prostate, and lung carcinoma cells. Shp2 knockdown and inactivation prevented tumor xenograft growth of these carcinoma cells. Biochemical analyses indicated that Shp2 inhibition suppressed Src, Erk1/2, and c-Myc activities, whereas it elevated p27 (CDKN1B) both in cell cultures and in tumors. These results suggest that Shp2 is a non-oncogene addiction gene critically involved in malignant growth of carcinoma and a potential target for development of a novel PTP-targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1630.