Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression
Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression
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DOI：
10.1101/gad.316304
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发表时间：
2004-12-15
影响因子：
10.5
通讯作者：
Frame, MC
中科院分区：
文献类型：
--
作者：
McLean, GW;Komiyama, NH;Frame, MC
我们已经产生了在角蛋白-14驱动的Cre与修饰的雌激素受体（CreER（T2））融合的控制下具有floxed fak等位基因的小鼠。4-羟基-他莫昔芬治疗诱导表皮中的fak缺失，并抑制化学诱导的皮肤肿瘤形成。一旦良性肿瘤形成，诱导fak的丢失抑制恶性进展。虽然fak缺失与体外角质形成细胞迁移减少有关，但我们发现对体内伤口再上皮化没有影响。然而，增加角质形成细胞的细胞死亡后，fak删除在体外和体内观察。我们的工作提供了第一个实验证据，表明FAK在肿瘤发生中，这是与增强凋亡。
We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to a modified estrogen receptor (CreER(T2)). 4-Hydroxy-tamoxifen treatment induced fak deletion in the epidermis, and suppressed chemically induced skin tumor formation. Loss of fak induced once benign tumors had formed inhibited malignant progression. Although fak deletion was associated with reduced migration of keratinocytes in vitro, we found no effect on wound re-epithelialization in vivo. However, increased keratinocyte cell death was observed after fak deletion in vitro and in vivo. Our work provides the first experimental proof implicating FAK in tumorigenesis, and this is associated with enhanced apoptosis.