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CD147‐targeting siRNA inhibits cell‐matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase
Author(s) -
NISHIBABA Rie,
HIGASHI Yuko,
SU Juan,
FURUKAWA Tatsuhiko,
KAWAI Kazuhiro,
KANEKURA Takuro
Publication year - 2012
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2011.01304.x
Subject(s) - basigin , focal adhesion , integrin , microbiology and biotechnology , cell adhesion , ptk2 , integrin linked kinase , phosphorylation , integrin, beta 6 , extracellular matrix , cell adhesion molecule , biology , chemistry , cell , protein kinase a , matrix metalloproteinase , biochemistry , mitogen activated protein kinase kinase , cyclin dependent kinase 2
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.