CD44 signaling through focal adhesion kinase and its anti‐apoptotic effect

FEBS Letters

Nakajima, Nobuyuki²  Higashi, Morihiro¹  Harigaya, Kenichi¹  Kitagawa, Motoo¹  Fujita, Yoshihisa¹  Koda, Keiji²  Ishii, Genichiro¹  Azuma, Kazuhiko¹  Kishi, Hirohisa¹  Hiwasa, Takaki³  Nakamura, Sukeyuki¹ 

[1] Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan

关键词: CD44;    Signal transduction;    Focal adhesion kinase;    Phosphatidylinositol 3-kinase;    Mitogen-activated protein kinase;    Apoptosis;    CD44E;    epithelial form of CD44;    FAK;    focal adhesion kinase;    PI3K;    phosphatidylinositol 3-kinase;    MAPK;    mitogen-activated protein kinase;    HA;    hyaluronan;    ECM;    extracellular matrix;    CD44s;    standard form of CD44;    mAb;    monoclonal antibody;    pTyr;    phosphotyrosine;    IMEM;    Iscove's modified Eagle's medium;    FBS;    fetal bovine serum;   

DOI  :  10.1016/S0014-5793(02)03262-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown