Overexpression of HAb18G/CD147 promotes invasion and metastasis via alpha3beta1 integrin mediated FAK-paxillin and FAK-PI3K-Ca2+ pathways.

Abstract	Mechanism of HAb18G/CD147 underlying the metastasis process of human hepatoma cells has not been determined. In the present study, we found that integrin alpha3beta1 colocalizes with HAb18G/CD147 in human 7721 hepatoma cells. The enhancing effect of HAb18G/CD147 on adhesion, invasion capacities and matrix metalloproteinases (MMPs) secretion was decreased by integrin alpha3beta1 antibodies (p<0.01). The expressions of integrin downstream molecules including focal adhesion kinase (FAK), phospho-FAK (p-FAK), paxillin, and phospho-paxillin (p-paxillin) were increased in human hepatoma cells overexpressing HAb18G/CD147. Deletion of HAb18G/CD147 reduces the quantity of focal adhesions and rearranges cytoskeleton. Wortmannin and LY294002, specific phosphatidylinositol kinase (PI3K) inhibitors, reversed the effect of HAb18G/CD147 on the regulation of intracellular Ca(2+) mobilization, significantly reducing cell adhesion, invasion and MMPs secretion potential (p<0.01). Together, these results suggest that HAb18G/CD147 enhances the invasion and metastatic potentials of human hepatoma cells via integrin alpha3beta1-mediated FAK-paxillin and FAKPI3K-Ca(2+) signal pathways.
Authors	J Tang, Y-M Wu, P Zhao, X-M Yang, J-L Jiang, Z-N Chen
Journal	Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 65 Issue 18 Pg. 2933-42 (Sep 2008) ISSN: 1420-682X [Print] Switzerland
PMID	18695939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BSG protein, human Integrin alpha3beta1 Paxillin Phosphoinositide-3 Kinase Inhibitors Basigin Focal Adhesion Protein-Tyrosine Kinases Calcium
Topics	Basigin (genetics, metabolism) Calcium (metabolism) Carcinoma, Hepatocellular (metabolism, pathology, secondary) Cell Line, Tumor Cytoskeleton (metabolism) Focal Adhesion Protein-Tyrosine Kinases (metabolism) Focal Adhesions (metabolism) Gene Silencing Humans Integrin alpha3beta1 (genetics, metabolism) Liver Neoplasms (metabolism, pathology) Neoplasm Invasiveness Neoplasm Metastasis Paxillin (metabolism) Phosphatidylinositol 3-Kinases (metabolism) Phosphoinositide-3 Kinase Inhibitors

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