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