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
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
收藏
页码:598 / 610
页数:13
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