CD44 signaling through focal adhesion kinase and its anti-apoptotic effect.
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.
Fujita
Yoshihisa
Y
Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Japan.
Kitagawa
Motoo
M
Nakamura
Sukeyuki
S
Azuma
Kazuhiko
K
Ishii
Genichiro
G
Higashi
Morihiro
M
Kishi
Hirohisa
H
Hiwasa
Takaki
T
Koda
Keiji
K
Nakajima
Nobuyuki
N
Harigaya
Kenichi
K
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D018960:Hyaluronan Receptors; D011994:Recombinant Proteins; D014443:Tyrosine; D005047:Etoposide; D006820:Hyaluronic Acid; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins