Differential regulation of cell motility and invasion by FAK

Journal of Cell Biology - Tập 160 Số 5 - Trang 753-767 - 2003
Datsun A. Hsia1, Satyajit K. Mitra1, Christof R. Hauck1,2, Daniel N. Streblow2, Jay A. Nelson2, Duško Ilić3, Shuang Huang1, Erguang Li1, Glen R. Nemerow1, Jixuan Leng1, Kathryn Spencer1, David A. Cheresh1, David D. Schlaepfer1
11Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
22Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201
33Department of Stomatology, University of California, San Francisco, CA 94143

Tóm tắt

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.

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Tài liệu tham khảo

1999, Oncogene., 18, 4718, 10.1038/sj.onc.1202850

2000, J. Cell Biol., 149, 741, 10.1083/jcb.149.3.741

2000, Curr. Biol., 10, 719, 10.1016/S0960-9822(00)00537-6

2000, Oncogene., 19, 580, 10.1038/sj.onc.1203338

2000, Biochem. J., 2, 241

2002, Oncogene., 21, 2347, 10.1038/sj.onc.1205298

2000, Clin. Cancer Res., 6, 2417

2002, Mol. Cell. Biol., 22, 2427, 10.1128/MCB.22.8.2427-2440.2002

2002, J. Biol. Chem., 277, 33857, 10.1074/jbc.M204429200

2001, Mol. Cell. Biol., 21, 7295, 10.1128/MCB.21.21.7295-7306.2001

2000, Cell., 103, 239, 10.1016/S0092-8674(00)00116-1

1998, Proc. Natl. Acad. Sci. USA., 95, 15394, 10.1073/pnas.95.26.15394

1998, EMBO J., 17, 81, 10.1093/emboj/17.1.81

1999, J. Cell Sci., 112, 947, 10.1242/jcs.112.6.947

2001, EMBO J., 20, 3437, 10.1093/emboj/20.13.3437

1995, Oncogene., 10, 1037

2001, J. Biol. Chem., 276, 17653, 10.1074/jbc.M009329200

2001, Cancer Res., 61, 7079

2002, J. Biol. Chem., 277, 12487, 10.1074/jbc.C100760200

2002, EMBO J., 21, 6289, 10.1093/emboj/cdf631

2002, Nat. Rev., 2, 91, 10.1038/nrc727

2002, J. Biol. Chem., 277, 27265, 10.1074/jbc.M203063200

2000, J. Biol. Chem., 275, 12266, 10.1074/jbc.275.16.12266

1995, Nature., 377, 539, 10.1038/377539a0

1998, J. Cell Biol., 143, 547, 10.1083/jcb.143.2.547

2001, Am. J. Pathol., 159, 93, 10.1016/S0002-9440(10)61677-X

2000, Oncogene., 19, 5636, 10.1038/sj.onc.1203912

1998, J. Biol. Chem., 273, 25673, 10.1074/jbc.273.40.25673

1998, Genes Dev., 12, 3331, 10.1101/gad.12.21.3331

1997, J. Cell Biol., 137, 481, 10.1083/jcb.137.2.481

1998, J. Cell Biol., 140, 961, 10.1083/jcb.140.4.961

2001, J. Cell Biol., 152, 97, 10.1083/jcb.152.1.97

1998, Head Neck., 20, 745, 10.1002/(SICI)1097-0347(199812)20:8<745::AID-HED14>3.0.CO;2-Z

1996, Cell., 84, 359, 10.1016/S0092-8674(00)81280-5

2000, J. Biol. Chem., 275, 14729, 10.1074/jbc.275.19.14729

1993, Mol. Cell. Biol., 13, 5225

2000, Mol. Med. Today., 6, 149, 10.1016/S1357-4310(00)01686-5

1999, J. Biol. Chem., 274, 21491, 10.1074/jbc.274.31.21491

1999, J. Cell Biol., 145, 1461, 10.1083/jcb.145.7.1461

1999, Mol. Cell. Biol., 19, 4806, 10.1128/MCB.19.7.4806

1995, Cancer Res., 55, 2752

2000, Eur. J. Cancer., 36, 1640, 10.1016/S0959-8049(00)00175-1

2002, J. Biol. Chem., 277, 26927, 10.1074/jbc.M202261200

2000, J. Cell Sci., 113, 3673, 10.1242/jcs.113.20.3673

1999, J. Cell Biol., 147, 611, 10.1083/jcb.147.3.611

2002, J. Cell. Biochem., 84, 377, 10.1002/jcb.10025

1994, EMBO J., 13, 3748, 10.1002/j.1460-2075.1994.tb06684.x

2001, Biochim. Biophys. Acta., 1540, 1, 10.1016/S0167-4889(01)00123-9

1994, Nature., 372, 786, 10.1038/372786a0

1997, Mol. Cell. Biol., 17, 1702, 10.1128/MCB.17.3.1702

1999, Prog. Biophys. Mol. Biol., 71, 435, 10.1016/S0079-6107(98)00052-2

1998, Cancer Res., 58, 900

2002, Biochim. Biophys. Acta., 8, 311

1999, J. Cell Sci., 112, 2677, 10.1242/jcs.112.16.2677

2000, Nat. Cell Biol., 2, 249, 10.1038/35010517

2001, Oncogene., 20, 1152, 10.1038/sj.onc.1204208

1999, Cell., 99, 511, 10.1016/S0092-8674(00)81539-1

1985, Exp. Cell Res., 159, 141, 10.1016/S0014-4827(85)80044-6

1999, J. Cell Sci., 112, 231, 10.1242/jcs.112.2.231

2002, J. Cell Biol., 157, 819, 10.1083/jcb.200112107

2001, J. Biol. Chem., 276, 16248, 10.1074/jbc.M010190200

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Journal of Cell Biology

Tập 160 Số 5

753-767

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