title: CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase.
abstract: CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co-localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked-down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix-coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK.
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Nishibaba
authors.forename: Yuko
authors.initials: Y
authors.lastname: Higashi
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kawai
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
mesh_terms: D051926:Basigin / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034741:RNA, Small Interfering
chemical_list: C497886:BSG protein, human; D019012:Integrin beta1; D034741:RNA, Small Interfering; D051926:Basigin; D051416:Focal Adhesion Protein-Tyrosine Kinases