Department of Biochemistry, The Rappaport Family Institute for Research in the Medical Sciences, Technion - Israel Institute of Technology, Haifa, Israel.
Anticancer Agents Med Chem. 2011 Sep;11(7):600-6. doi: 10.2174/187152011796817673.
Recent studies connect the FAK and Wnt/β-catenin signaling pathways, both which promote cancer when aberrantly activated in mammalian cells. Over-stimulation of either Wnt/β-catenin or FAK activities was independently shown to promote numerous types of human cancers, including colon, breast, prostate and ovary. Observations in different model systems suggest a complex and dynamic cross-talk between these two pathways. During early vertebrate development, FAK protein is required for the proper regulation of Wnt/β- catenin signaling that controls pattern formation in the developing nervous system. In Xenopus laevis embryos, FAK protein depletion eliminated Wnt3a gene expression in the neural plate. In mouse osteoclast cells, mechanical stimulation through FAK activation stabilized β-catenin protein to promote its nuclear translocation. In contrast, in the mouse intestine, FAK activity was induced downstream of Wnt to promote intestinal regeneration and was also essential for tumorigenesis in an APC deletion model of colorectal cancer. Adding to this complexity, in human cell lines, FAK induced a context-dependent modulation of Wnt signaling to activate target-gene expression. Other diseases are also associated with FAK and Wnt pathway over-activation. Increased FAK and Wnt pathway activities were independently implicated in idiopathic pulmonary fibrosis (IPF), a lung disease of unknown etiology. Revealing the FAK-Wnt connection in IPF could provide a better understanding of disease pathology. There appear to be multiple interactions between the Wnt/β-catenin and FAK signaling pathways in different cell types and organisms. Mutual FAK-Wnt pathway regulation could be a general phenomenon, having many still undetermined roles in either normal physiological or disease processes.
最近的研究将 FAK 和 Wnt/β-连环蛋白信号通路联系起来，这两条通路在哺乳动物细胞中异常激活时都会促进癌症。独立研究表明，Wnt/β-连环蛋白或 FAK 活性的过度刺激均可促进多种人类癌症，包括结肠癌、乳腺癌、前列腺癌和卵巢癌。在不同的模型系统中的观察表明，这两条通路之间存在着复杂而动态的相互作用。在早期脊椎动物发育过程中，FAK 蛋白对于正确调节 Wnt/β-连环蛋白信号通路是必需的，该信号通路控制着神经系统的发育模式形成。在非洲爪蟾胚胎中，FAK 蛋白的耗竭消除了神经板中的 Wnt3a 基因表达。在小鼠破骨细胞中，通过 FAK 激活的机械刺激稳定了β-连环蛋白蛋白，促进其核易位。相比之下，在小鼠肠道中，Wnt 下游的 FAK 活性诱导了促进肠道再生的作用，并且在 APC 缺失的结直肠癌模型中对肿瘤发生也是必不可少的。使情况更加复杂的是，在人类细胞系中，FAK 诱导了 Wnt 信号的上下文依赖性调节，以激活靶基因表达。其他疾病也与 FAK 和 Wnt 途径的过度激活有关。在特发性肺纤维化（IPF），一种病因不明的肺部疾病中，FAK 和 Wnt 途径的活性均独立增加。揭示 IPF 中的 FAK-Wnt 联系可以更好地了解疾病的病理生理学。在不同的细胞类型和生物体中，Wnt/β-连环蛋白和 FAK 信号通路之间似乎存在多种相互作用。FAK-Wnt 途径的相互调节可能是一种普遍现象，在正常生理或疾病过程中具有许多尚未确定的作用。
