Phosphatidylinositol phosphate 5-kinase I?i2 in association with Src controls anchorage-independent growth of tumor cells.

ABSTRACT: A fundamental property of tumor cells is to defy anoikis, cell death caused by a lack of cell-matrix interaction, and grow in an anchorage-independent manner. How tumor cells organize signaling molecules at the plasma membrane to sustain oncogenic signals in the absence of cell-matrix interactions remains poorly understood. Here, we describe a role for phosphatidylinositol 4-phosphate 5-kinase (PIPK) I?i2 in controlling anchorage-independent growth of tumor cells in coordination with the proto-oncogene Src. PIPKI?i2 regulated Src activation downstream of growth factor receptors and integrins. PIPKI?i2 directly interacted with the C-terminal tail of Src and regulated its subcellular localization in concert with talin, a cytoskeletal protein targeted to focal adhesions. Co-expression of PIPKI?i2 and Src synergistically induced the anchorage-independent growth of nonmalignant cells. This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKI?i2, functions with the proto-oncogene Src, to regulate oncogenic signaling.

SUBMITTER: Thapa N 

PROVIDER: S-EPMC3843082 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature