Phosphatidylinositol phosphate 5-kinase Iγi2 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) Iγi2 in controlling anchorage-independent growth of tumor cells in coordination with the proto-oncogene 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.

• Authors: Narendra Thapa, Suyong Choi, Andrew Hedman, Xiaojun Tan, Richard A Anderson
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 288 Issue 48 Pg. 34707-18 (Nov 29 2013) ISSN: 1083-351X [Electronic] United States
• PMID: 24151076 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MAS1 protein, human
• Phosphatidylinositol 4,5-Diphosphate
• Phosphatidylinositols
• Proto-Oncogene Mas
• Talin
• Phosphotransferases (Alcohol Group Acceptor)
• 1-phosphatidylinositol-4-phosphate 5-kinase

Topics

• Amino Acid Sequence
• Animals
• Anoikis (genetics)
• Cell Proliferation
• Focal Adhesions (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Genes, src (genetics)
• HEK293 Cells
• Humans
• Mice
• NIH 3T3 Cells
• Neoplasms (genetics, metabolism, pathology)
• Phosphatidylinositol 4,5-Diphosphate (metabolism)
• Phosphatidylinositols (metabolism)
• Phosphotransferases (Alcohol Group Acceptor) (genetics, metabolism)
• Proto-Oncogene Mas
• Signal Transduction (genetics)
• Talin (metabolism)