Differential regulation of cell motility and invasion by FAK

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2003
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Hsia, Datsun A.
Mitra, Satyajit K.
Streblow, Daniel N.
Nelson, Jay A.
Ilić, Du ko
Huang, Shuang
Li, Erguang
Nemerow, Glen R.
Leng, Jay
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Journal of Cell Biology. 2003, 160(5), pp. 753-767. ISSN 0021-9525. eISSN 1540-8140. Available under: doi: 10.1083/jcb.200212114
Zusammenfassung

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.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
motility, invasion, FAK, Src, JNK
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Zitieren
ISO 690HSIA, Datsun A., Satyajit K. MITRA, Christof R. HAUCK, Daniel N. STREBLOW, Jay A. NELSON, Du ko ILIĆ, Shuang HUANG, Erguang LI, Glen R. NEMEROW, Jay LENG, Kathryn S. R. SPENCER, David A. CHERESH, David D. SCHLAEPFER, 2003. Differential regulation of cell motility and invasion by FAK. In: Journal of Cell Biology. 2003, 160(5), pp. 753-767. ISSN 0021-9525. eISSN 1540-8140. Available under: doi: 10.1083/jcb.200212114
BibTex
@article{Hsia2003Diffe-7535,
  year={2003},
  doi={10.1083/jcb.200212114},
  title={Differential regulation of cell motility and invasion by FAK},
  number={5},
  volume={160},
  issn={0021-9525},
  journal={Journal of Cell Biology},
  pages={753--767},
  author={Hsia, Datsun A. and Mitra, Satyajit K. and Hauck, Christof R. and Streblow, Daniel N. and Nelson, Jay A. and Ilić, Du ko and Huang, Shuang and Li, Erguang and Nemerow, Glen R. and Leng, Jay and Spencer, Kathryn S. R. and Cheresh, David A. and Schlaepfer, David D.}
}
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