Cooperative Roles of Fyn and Cortactin in Cell Migration of Metastatic Murine Melanoma

Src family kinases are major regulators of various integrin-mediated biological processes, although their functional roles and substrates in cancer metastasis are unknown. We explored the roles of Src family tyrosine kinases in cell migration and the spread of K-1735 murine melanoma cell lines with...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-11, Vol.278 (48), p.48367-48376
Main Authors: Huang, Jinhong, Asawa, Tamae, Takato, Tsuyoshi, Sakai, Ryuichi
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cell Membrane - metabolism
Cell Movement
Cortactin
Detergents - pharmacology
DNA-Binding Proteins - metabolism
Fibroblasts - metabolism
Fibronectins - chemistry
Fibronectins - metabolism
Fyn protein
Immunoblotting
Integrins - metabolism
Melanoma - metabolism
Melanoma - pathology
Mice
Microfilament Proteins - metabolism
Microfilament Proteins - physiology
Octoxynol - pharmacology
Phosphorylation
Plant Proteins - metabolism
Polylysine - chemistry
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-fyn
Signal Transduction
Time Factors
Tyrosine - metabolism
Up-Regulation
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Summary:Src family kinases are major regulators of various integrin-mediated biological processes, although their functional roles and substrates in cancer metastasis are unknown. We explored the roles of Src family tyrosine kinases in cell migration and the spread of K-1735 murine melanoma cell lines with low or high metastatic potential. Corresponding to elevated cell motility and spreading ability, Fyn was selectively activated among Src family kinases, and the cell motility was blocked by an inhibitor of Src family kinases. Significant tyrosine phosphorylation of cortactin, stable complex formation between activated Fyn and cortactin, and co-localization of cortactin with Fyn at cell membranes were all observed only in cells with high metastatic potential. Both integrin-mediated Fyn activation and hyperphosphorylation of cortactin were observed 2–5 h after stimulation in highly metastatic cells, and they required de novo protein synthesis. We demonstrate that cortactin is a specific substrate and cooperative effector of Fyn in integrin-mediated signaling processes regulating metastatic potential.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M308213200