Focal adhesion kinase: a prominent determinant in breast cancer initiation, progression and metastasis.
Focal adhesion kinase: a prominent determinant in breast cancer initiation, progression and metastasis.
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DOI：
10.1016/j.canlet.2009.07.005
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发表时间：
2010-03-28
期刊：
影响因子：
9.7
通讯作者：
Guan, Jun-Lin
中科院分区：
文献类型：
--
作者：
Luo, Ming;Guan, Jun-Lin
粘着斑激酶（FAK）是一种细胞内非受体酪氨酸激酶。除了其作为整合素信号转导的主要介体的作用之外，FAK还通过广泛的细胞外刺激物参与信号传导，所述细胞外刺激物包括生长因子、G蛋白偶联受体激动剂、细胞因子和其它炎症介体。FAK与乳腺癌之间的联系是由大量的报告表明，FAK基因扩增和过表达在很大一部分乳腺癌标本强烈建议。此外，FAK表达和活性增加常常与转移性疾病和预后不良相关。自20世纪90年代初发现以来，大量研究表明FAK在调节细胞铺展、粘附、迁移、存活、增殖、分化和血管生成中的作用。许多在培养细胞中的这些研究提供了强有力的证据，将FAK表达/活化与癌症的促进联系起来。近年来，FAK在促进乳腺肿瘤发生、发展和转移中的重要作用已被不同的人类乳腺癌动物模型所揭示，包括免疫缺陷啮齿动物的异种移植模型和在胚胎或出生后发育期间在乳腺上皮细胞中特异性缺失FAK的转基因小鼠的自发性肿瘤模型。这些体内研究确立了FAK作为乳腺癌发生、进展和转移的重要决定因素。此外，近年来有研究发现FAK在体内具有维持乳腺癌干/祖细胞的功能，这可能为FAK促进乳腺癌发生发展提供了新的细胞学机制。近20年来对FAK的研究积累了丰富的知识，这将有助于设计潜在的乳腺癌新疗法。
Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase. In addition to its role as a major mediator of signal transduction by integrins, FAK also participates in signaling by a wide range of extracellular stimuli including growth factors, G-protein coupled receptor agonists, cytokines, and other inflammatory mediators. The link between FAK and breast cancers is strongly suggested by a number of reports showing that FAK gene is amplified and overexpressed in a large fraction of breast cancer specimens. In addition, increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Since its discovery in early 1990s, numerous studies have shown a role for FAK in the regulation of cell spreading, adhesion, migration, survival, proliferation, differentiation, and angiogenesis. Many of these studies in cultured cells provided strong evidence to connect FAK expression/activation to the promotion of cancer. Recently, a prominent role of FAK in promoting mammary tumorigenesis, progression and metastasis has been unveiled by different animal models of human breast cancer, including xenograft models in immunodeficient rodents and spontaneous tumor models in transgenic mice that have specific deletion of FAK in the mammary epithelial cells during embryonic or postnatal development. These in vivo studies established FAK as a prominent determinant in mammary cancer initiation, progression and metastasis. Furthermore, a novel function of FAK in maintaining mammary cancer stem/progenitor cells in vivo has been recently reported, which may provide a novel cellular mechanism of FAK in promoting breast cancer initiation and progression. The wealth of knowledge accumulated over almost two decades of research on FAK should help to design potentially novel therapies for breast cancer.
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DOI：
10.1083/jcb.200504124
发表时间：
2005-11-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Benlimame N;He Q;Jie S;Xiao D;Xu YJ;Loignon M;Schlaepfer DD;Alaoui-Jamali MA
通讯作者：
Alaoui-Jamali MA
影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
8
作者：
Agochiya, M;Brunton, VG;Frame, MC
通讯作者：
Frame, MC
影响因子：
4.8
作者：
Bailey, Kelly M.;Liu, Jun
通讯作者：
Liu, Jun
影响因子：
4.8
作者：
Chan, PC;Lai, JF;Chen, HC
通讯作者：
Chen, HC