CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase
Article first published online: 3 OCT 2011
© 2011 Japanese Dermatological Association
The Journal of Dermatology
Special Issue: Hair Biology and Hair Loss Disorders (pages 1-41)
Volume 39, Issue 1, pages 63–67, January 2012
How to Cite
NISHIBABA, R., HIGASHI, Y., SU, J., FURUKAWA, T., KAWAI, K. and KANEKURA, T. (2012), CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase. The Journal of Dermatology, 39: 63–67. doi: 10.1111/j.1346-8138.2011.01304.x
- Issue published online: 29 DEC 2011
- Article first published online: 3 OCT 2011
- Received 28 February 2011; accepted 30 April 2011.
- cell-matrix adhesion;
- focal adhesion kinase;
- integrin β1;
- malignant melanoma
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.