Abstract LB-132: Protein interactome between PTEN and cancer-associated mutant demonstrated the regulatory pathway of migration through its novel interactors

Mutation of the PTEN tumor suppressor protein frequently occurs in a variety of human cancers. PTEN is a phosphatase that negatively regulates the phosphatidyl-inositol-3-kinase (PI3K) pathway, and regulates cell proliferation, apoptosis, and cell motility. Though the tumor suppressive function involves PTEN9s lipid phosphatase-dependent and -independent activities, the mechanism leading to the phosphatase-independent function of PTEN is poorly understood. Some PTEN mutants have lipid phosphatase activity but fail to suppress cell growth. Here we use a cancer associated mutant, G20E, to gain insight into the phosphatase-independent function of PTEN by investigating protein-protein interactions using mass spectrometry (MS)-based stable isotope labeling by amino acids in cell culture (SILAC). A strategy named parallel affinity purification (PAP) and SILAC has been developed to prioritize interactors and to compare the interactions between wild-type and G20E PTEN. Clustering of the prioritized interactors acquired by the PAP-SILAC approach are mainly involved in cell migration and apoptosis pathways, suggesting deregulation of the pathways could be involved in the tumorigenesis derived by the PTEN mutant. We further demonstrate that the one of wild-type specific interactor is required for the regulatory function of wild-type PTEN in cell migration. Furthermore, the other wild type specific interactor affects cell growth. These finding contribute to a better understanding of the mechanisms of PTEN9s functions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-132. doi:10.1158/1538-7445.AM2011-LB-132