CD44 signaling through focal adhesion kinase and its anti-apoptotic effect |
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Authors: | Fujita Yoshihisa Kitagawa Motoo Nakamura Sukeyuki Azuma Kazuhiko Ishii Genichiro Higashi Morihiro Kishi Hirohisa Hiwasa Takaki Koda Keiji Nakajima Nobuyuki Harigaya Kenichi |
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Affiliation: | Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Japan. |
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Abstract: | Adhesion molecules can initiate intracellular signaling. Engagement of CD44 either by its natural ligand hyaluronan or a specific antibody on a cell line induced tyrosine phosphorylation and activation of focal adhesion kinase (FAK), which then associated with phosphatidylinositol 3-kinase (PI3K) and activated mitogen-activated protein kinase at its downstream. However, the introduction of dominant negative Rho into the cells inhibited the CD44-stimulated FAK phosphorylation. Cells expressing CD44 were significantly resistant to etoposide-induced apoptosis. This anti-apoptotic effect was cancelled by the inhibition of either Rho, FAK or PI3K. These results may indicate a signaling pathway from CD44 to mediate the resistance against drug-induced apoptosis in cancer cells. |
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