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PIPKI? regulates focal adhesion dynamics and colon cancer cell invasion.

ABSTRACT: Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type I? (PIPKI?) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKI? promoted focal adhesion formation, whereas cells expressing either PIPKI?(K188,200R) or PIPKI?(D316K), two kinase-dead mutants, had much fewer focal adhesions than those expressing WT PIPKI? in CHO-K1 cells and HCT116 colon cancer cells. Furthermore, overexpression of PIPKI?, but not PIPKI?(K188,200R), resulted in an increase in both focal adhesion assembly and disassembly rates. Depletion of PIPKI? by using shRNA strongly inhibited formation of focal adhesions in HCT116 cells. Overexpression of PIPKI?(K188,200R) or depletion of PIPKI? reduced the strength of HCT116 cell adhesion to fibronection and inhibited the invasive capacities of HCT116 cells. PIPKI? depletion reduced PIP? levels to ?40% of control and PIP? to undetectable levels, and inhibited vinculin localizing to focal adhesions. Taken together, PIPKI? positively regulates focal adhesion dynamics and cancer invasion, most probably through PIP?-mediated vinculin activation.

SUBMITTER: Wu Z

PROVIDER: S-EPMC3171478 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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PIPKIγ regulates focal adhesion dynamics and colon cancer cell invasion.

Wu Zhaofei Z Li Xiang X Sunkara Manjula M Spearman Heather H Morris Andrew J AJ Huang Cai C

PloS one 20110912 9

Focal adhesion assembly and disassembly are essential for cell migration and cancer invasion, but the detailed molecular mechanisms regulating these processes remain to be elucidated. Phosphatidylinositol phosphate kinase type Iγ (PIPKIγ) binds talin and is required for focal adhesion formation in EGF-stimulated cells, but its role in regulating focal adhesion dynamics and cancer invasion is poorly understood. We show here that overexpression of PIPKIγ promoted focal adhesion formation, whereas ...[more]

PMID: 21931851

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Project description:Ovarian cancer is as a major contributor to gynaecologic death globally. The present study aimed to investigate the regulatory role of spectrin β non-erythrocytic 2 gene (SPTBN2) in endometroid ovarian cancer and its mechanism of action. According to the Gene Expression Profiling Interactive Analysis (GEPIA) database, SPTBN2 expression is elevated in ovarian cancer tissues and higher SPTBN2 expression indicated a worse prognosis. The present study assessed SPTBN2 mRNA and protein expression levels by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability, proliferation, migration and invasion were assessed with Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays, respectively. SPTBN2 expression was notably enhanced in ovarian cancer cell lines, especially in A2780 cells compared with HOSEPiC cells (P<0.001). Following transfection with small interfering (si)RNA targeting SPTBN2, the viability, proliferation, migration and invasion of A2780 cells were decreased compared with those of A2780 cells transfected with siRNA-NC (P<0.001). Gene Set Enrichment Analysis database revealed that SPTBN2 was primarily enriched in 'focal adhesion' and 'extracellular matrix (ECM)-receptor interaction', whereas SPTBN2 was significantly associated with integrin β4 (ITGB4) in the GEPIA database. In addition, rescue experiments were performed to determine the mechanism of SPTBN2 in endometroid ovarian cancer. ITGB4 overexpression reversed the inhibitory effects of the SPTBN2 knockdown on viability, proliferation, migration and invasion of A2780 cells (P<0.05). The impacts of SPTBN2 on the expression of focal adhesion and downstream ECM receptor signalling-related proteins, including Src and p-FAK/FAK, were significantly reversed by ITGB4 overexpression (P<0.01). Collectively, SPTBN2 may regulate endometroid ovarian cancer cell proliferation, invasion and migration through the ITGB4-mediated focal adhesion and ECM receptor signalling pathway.

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PIPKI? regulates focal adhesion dynamics and colon cancer cell invasion.

Publications

PIPKIγ regulates focal adhesion dynamics and colon cancer cell invasion.

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