Subsequent activation of mitogen-activated protein kinase after adhesion of transitional cell cancer cells to fibronectin.
BACKGROUND
In the process of tumor invasion and metastasis, interactions between tumor cells and extracellular matrix play a crucial role. Recently, it was shown that fibronectin binding to fibronectin receptor promotes mitogen-activated protein kinase (MAPK) activation after tyrosine phosphorylation of focal adhesion kinase (FAK). We investigated these signal transduction events in transitional cell cancer (TCC) cells.


METHODS
(1) The adhesion of T24 cells, a fibronectin-receptor-positive TCC cell line, to fibronectin was investigated; (2) the MAPK activation after fibronectin stimulation in bladder cancer cell lines was examined by Western blotting using an antiactive MAPK antibody, and (3) FAK, Sos, and Grb-2 were also examined by Western blot analysis.


CONCLUSIONS
T24 cells adhered to fibronectin-coated dishes more quickly than to the noncoated dishes. Fibronectin stimulation induced activation of MAPK in T24, SCaBER, and HT1376 cells. However, activated MAPK was not detected in RT4 cells which do not express alpha(5)beta(1) integrin (major fibronectin receptor) after fibronectin stimulation. T24, SCaBER, and HT1376 expressed FAK and Sos. RT4 showed little FAK and Sos expression. Grb-2 was expressed in all cell lines. Adhesion of fibronectin-receptor-positive TCC cells to fibronectin activates the MAPK cascade, possibly resulting in activation of tumor cells.
Department of Urology, Niigata Cancer Center Hospital, Niigata, Japan. urotoshi@niigata-cc.niigata.niigata.jp
Toshihiro
T
Saito
Yoshihiko
Y
Tomita
Takashi
T
Kawasaki
Vladimir
V
Bilim
Kota
K
Takahashi
D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D005353:Fibronectins / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
D005353:Fibronectins; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases