FAK in cancer: mechanistic findings and clinical applications

被引：1060

作者：

Sulzmaier, Florian J. ^{[1
]}

Jean, Christine ^{[1
]}

Schlaepfer, David D. ^{[1
]}

机构：

[1] Univ Calif San Diego, Moores Canc Ctr, Dept Reprod Med, La Jolla, CA 92093 USA

来源：

NATURE REVIEWS CANCER | 2014年 / 14卷 / 09期

基金：

美国国家卫生研究院;

关键词：

FOCAL-ADHESION KINASE; EPITHELIAL-MESENCHYMAL TRANSITION; SQUAMOUS-CELL CARCINOMA; ENDOTHELIAL FAK; DEPENDENT FUNCTIONS; THERAPEUTIC TARGET; BARRIER FUNCTION; E-CADHERIN; CONDITIONAL DELETION; CRYSTAL-STRUCTURES;

D O I：

10.1038/nrc3792

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. FAK promotes tumour progression and metastasis through effects on cancer cells, as well as stromal cells of the tumour microenvironment. The kinase-dependent and kinase-independent functions of FAK control cell movement, invasion, survival, gene expression and cancer stem cell self-renewal. Small molecule FAK inhibitors decrease tumour growth and metastasis in several preclinical models and have initial clinical activity in patients with limited adverse events. In this Review, we discuss FAK signalling effects on both tumour and stromal cell biology that provide rationale and support for future therapeutic opportunities.

引用

页码：598 / 610

页数：13

共 141 条

[1]

Angelucci A, 2007, CURR PHARM DESIGN, V13, P2129

[2] Loss of Focal Adhesion Kinase Enhances Endothelial Barrier Function and Increases Focal Adhesions [J].

Arnold, Kimberly M. ;

Goeckeler, Zoe M. ;

Wysolmerski, Robert B. .

MICROCIRCULATION, 2013, 20 (07) :637-649

[3] Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling [J].

Ashton, Gabrielle H. ;

Morton, Jennifer P. ;

Myant, Kevin ;

Phesse, Toby J. ;

Ridgway, Rachel A. ;

Marsh, Victoria ;

Wilkins, Julie A. ;

Athineos, Dimitris ;

Muncan, Vanesa ;

Kemp, Richard ;

Neufeld, Kristi ;

Clevers, Hans ;

Brunton, Valerie ;

Winton, Douglas J. ;

Wang, Xiaoyan ;

Sears, Rosalie C. ;

Clarke, Alan R. ;

Frame, Margaret C. ;

Sansom, Owen J. .

DEVELOPMENTAL CELL, 2010, 19 (02) :259-269

[4] Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling [J].

Avizienyte, E ;

Wyke, AW ;

Jones, RJ ;

McLean, GW ;

Westhoff, MA ;

Brunton, VG ;

Frame, MC .

NATURE CELL BIOLOGY, 2002, 4 (08) :632-638

[5] A FAK-Cas-Rac-Lamellipodin Signaling Module Transduces Extracellular Matrix Stiffness into Mechanosensitive Cell Cycling [J].

Bae, Yong Ho ;

Mui, Keeley L. ;

Hsu, Bernadette Y. ;

Liu, Shu-Lin ;

Cretu, Alexandra ;

Razinia, Ziba ;

Xu, Tina ;

Pure, Ellen ;

Assoian, Richard K. .

SCIENCE SIGNALING, 2014, 7 (330)

[6] Sunitinib and PF-562,271 (FAK/Pyk2 inhibitor) effectively block growth and recovery of human hepatocellular carcinoma in a rat xenograft model [J].

Bagi, Cedo M. ;

Christensen, James ;

Cohen, Darrel P. ;

Roberts, Walter G. ;

Wilkie, Dean ;

Swanson, Terri ;

Tuthill, Theresa ;

Andresen, Catharine J. .

CANCER BIOLOGY & THERAPY, 2009, 8 (09) :856-865

[7] Caspase-8 Association with the Focal Adhesion Complex Promotes Tumor Cell Migration and Metastasis [J].

Barbero, Simone ;

Mielgo, Ainhoa ;

Torres, Vicente ;

Teitz, Tal ;

Shields, David J. ;

Mikolon, David ;

Bogyo, Matthew ;

Barila, Daniela ;

Lahti, Jill M. ;

Schlaepfer, David ;

Stupack, Dwayne G. .

CANCER RESEARCH, 2009, 69 (09) :3755-3763

[8] Tumor-Secreted LOXL2 Activates Fibroblasts through FAK Signaling [J].

Barker, Holly E. ;

Bird, Demelza ;

Lang, Georgina ;

Erler, Janine T. .

MOLECULAR CANCER RESEARCH, 2013, 11 (11) :1425-1436

[9] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[10]

Bolós V, 2010, ONCOTARGETS THER, V3, P83

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