title: 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.affiliation: From the School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin 53706.
authors.forename: Narendra
authors.initials: N
authors.lastname: Thapa
authors.forename: Suyong
authors.initials: S
authors.lastname: Choi
authors.forename: Andrew
authors.initials: A
authors.lastname: Hedman
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023102:Anoikis / Q000235:genetics; D049109:Cell Proliferation; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016391:Genes, src / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000235:genetics; D016608:Talin / Q000378:metabolism
chemical_list: C000715470:MAS1 protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D000090063:Proto-Oncogene Mas; D016608:Talin; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase
keywords: Anchorage-independent Growth; Cancer Biology; Cell Growth; Oncogene; Phosphatidylinositol; Src; Talin