Phosphatidylinositol phosphate 5-kinase Iγi2 in association with src controls anchorage-independent growth of tumor cells

Narendra Thapa, Suyong Choi, Andrew Hedman, Xiaojun Tan, Richard A. Anderson

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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) Iγi2 in controlling anchorage-independent growth of tumor cells in coordination with the protooncogene Src. PIPKIγi2 regulated Src activation downstream of growth factor receptors and integrins. PIPKIγi2 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 PIPKIγi2 and Src synergistically induced the anchorage-independent growth of nonmalignant cells. This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKIγi2, functions with the proto-oncogene Src, to regulate oncogenic signaling.

Original languageEnglish (US)
Pages (from-to)34707-34718
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number48
DOIs
StatePublished - Nov 29 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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