Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway

• DOI: 10.1038/srep27391
• Publication Date: 2016-06-07T10:13:53Z
• Authors: Ae Lee Jeong; Sora Han; Sunyi Lee; Jeong Su Park; Yiling Lu; Shuangxing Yu; Jane Li; Kyung-Hee Chun; Gordon B. Mills; Young Yang
• Keywords: 0301 basic medicine; MAP Kinase Signaling System; Proto-Oncogene Proteins c-jun; Proto-Oncogene Proteins pp60(c-src); Mutation*; 610; Endometrial Neoplasms/pathology; Article; Ovarian Neoplasms/genetics; 03 medical and health sciences; Neoplasm Metastasis/genetics*; Protein Phosphatase 2/genetics*; Ovarian Neoplasms/pathology; Humans; Protein Phosphatase 2; Neoplasm Metastasis; Phosphorylation; Cell Proliferation; Ovarian Neoplasms; Endometrial Neoplasms; 3. Good health; Proto-Oncogene Proteins c-jun/metabolism*; Mutation; Proto-Oncogene Proteins pp60(c-src)/metabolism*; MAP Kinase Signaling System*; Female; Endometrial Neoplasms/genetics

Abstract Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but low ovarian clear cell carcinoma. However, the biological role mutation and cancer progression remains unclear. In this study, we found that expression is elevated high-grade primary tumor patients with papillary tumors ovary. To determine whether increased levels or might contribute to progression, effects overexpression on proliferation, migration, PP2A phosphatase activity were investigated using lines. Among mutations, PPP2R1A-W257G enhanced migration vitro through activating SRC-JNK-c-Jun pathway. Overexpression wild type (WT) its binding ability B56 regulatory subunits, whereas PPP2R1A-mutations lost bind most subunits except B56δ. Total PPP2R1A-associated PP2Ac significantly cells overexpressing PPP2R1A-WT. addition, PPP2R1A-WT proliferation growth vivo.