Focal adhesion kinase is required for β-catenin-induced mobilization of epidermal stem cells
Focal adhesion kinase is required for β-catenin-induced mobilization of epidermal stem cells
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DOI：
10.1093/carcin/bgs284
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发表时间：
2012-12-01
期刊：
影响因子：
4.7
通讯作者：
Brunton, Valerie G.
中科院分区：
文献类型：
--
作者：
Ridgway, Rachel A.;Serrels, Bryan;Brunton, Valerie G.
粘着斑激酶（FAK）是整合整合素和生长因子活化下游信号的非受体酪氨酸激酶。以前，我们已经证明，皮肤特异性fak的损失，防止化学诱导的小鼠皮肤癌后佛波酯治疗。在这项研究中，我们发现皮肤特异性fak的缺失阻止了毛囊隆起区域内干细胞的动员，这是佛波醇酯治疗后乳头状瘤的前体。我们还表明，佛波酯治疗的结果在激活的-连环蛋白在皮肤和FAK是必需的-连环蛋白诱导的干细胞动员。此外，抑制Src激酶活性（FAK的主要结合伴侣）也可阻止干细胞动员。我们发现，FAK是必需的核定位的-连环蛋白在皮肤中的佛波酯治疗和转录激活的-连环蛋白靶基因c-Myc。这提供了整合素和Wnt信号通路在控制表皮干细胞和与皮肤癌发生相关的早期事件中相互作用的第一个证据。
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that integrates signals downstream of integrin and growth factor activation. Previously, we have shown that skin-specific loss of fak prevents chemically induced skin carcinogenesis in mice following phorbol ester treatment. In this study, we show that skin-specific deletion of fak prevents mobilization of stem cells within the bulge region of the hair follicle, which are the precursors of papillomas following phorbol ester treatment. We also show that phorbol ester treatment results in activation of-catenin within the skin and that FAK is required for -catenin-induced stem cell mobilization. In addition, inhibition of Src kinase activity, a major binding partner of FAK also prevents stem cell mobilization. We show that FAK is required for the nuclear localization of -catenin in the skin following phorbol ester treatment and the transcriptional activation of the -catenin target gene c-Myc. This provides the first evidence of cross-talk between integrin and Wnt signalling pathways in the control of epidermal stem cells and the early events associated with skin carcinogenesis.