Mutation of Y925F in focal adhesion kinase (FAK) suppresses melanoma cell proliferation and metastasis.
This study focused on the role of focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase important for many cellular processes, in the proliferation, adhesion, and invasion of melanoma cells in vitro and in vivo. We found that the Y925F-mutation of FAK in B16F10 melanoma cells suppressed metastasis in an experimental model, which correlated well with decreased extracellular matrix dependent proliferative capability, adhesive, migrational, and invasive capabilities. Transduction of the mutation Y925F resulted in a down-regulation of the phosphorylation of Erk, the expression of VEGF, and the association of FAK with paxillin. The results provide clear evidence that 925Y of FAK is critical for melanoma metastasis and this phosphorylation site will be an anti-metastatic target.
Kaneda
Tomonori
T
Faculty of Pharmacy, Keio University, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512, Japan.
Sonoda
Yoshiko
Y
Ando
Kumi
K
Suzuki
Takaharu
T
Sasaki
Yasuhiro
Y
Oshio
Tomoyuki
T
Tago
Megumi
M
Kasahara
Tadashi
T
D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D008546:Melanoma, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C496061:PXN protein, human; D051419:Paxillin; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases