Differential regulation of cell motility and invasion by FAK

Datsun A. Hsia, Satyajit K. Mitra, Christof R. Hauck, Daniel N. Streblow, Jay A. Nelson, Dusko Ilic, Shuang Huang, Erguang Li, Glen R. Nemerow, Jay Leng, Kathryn S.R. Spencer, David A. Cheresh, David D. Schlaepfer

Research output: Contribution to journalArticle

421 Scopus citations

Abstract

Cell migration and invasion are fundamental components of tumor cell metastasis. Increased focal adhesion kinase (FAK) expression and tyrosine phosphorylation are connected with elevated tumorigenesis. Null mutation of FAK results in embryonic lethality, and FAK-/- fibroblasts exhibit cell migration defects in culture. Here we show that viral Src (v-Src) transformation of FAK-/- cells promotes integrin-stimulated motility equal to stable FAK reexpression. However, FAK-/- v-Src cells were not invasive, and FAK reexpression, Tyr-397 phosphorylation, and FAK kinase activity were required for the generation of an invasive cell phenotype. Cell invasion was linked to transient FAK accumulation at lamellipodia, formation of a FAK-Src-p130Cas-Dock180 signaling complex, elevated Rac and c-Jun NH2-terminal kinase activation, and increased matrix metalloproteinase expression and activity. Our studies support a dual role for FAK in promoting cell motility and invasion through the activation of distinct signaling pathways.

Original languageEnglish (US)
Pages (from-to)753-767
Number of pages15
JournalJournal of Cell Biology
Volume160
Issue number5
DOIs
StatePublished - Mar 3 2003

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Keywords

  • FAK
  • Invasion
  • JNK
  • Motility
  • Src

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hsia, D. A., Mitra, S. K., Hauck, C. R., Streblow, D. N., Nelson, J. A., Ilic, D., Huang, S., Li, E., Nemerow, G. R., Leng, J., Spencer, K. S. R., Cheresh, D. A., & Schlaepfer, D. D. (2003). Differential regulation of cell motility and invasion by FAK. Journal of Cell Biology, 160(5), 753-767. https://doi.org/10.1083/jcb.200212114