FAK and WNT Signaling: The Meeting of Two Pathways in Cancer and Development
FAK and WNT Signaling: The Meeting of Two Pathways in Cancer and Development
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DOI：
10.2174/187152011796817673
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发表时间：
2011-09-01
影响因子：
2.8
通讯作者：
Frank, Dale
中科院分区：
文献类型：
--
作者：
Fonar, Yuri;Frank, Dale
最近的研究将 FAK 和 Wnt/β-catenin 信号通路联系起来，这两种信号通路在哺乳动物细胞中异常激活时都会促进癌症。独立显示，Wnt/β-连环蛋白或 FAK 活性的过度刺激会促进多种类型的人类癌症，包括结肠癌、乳腺癌、前列腺癌和卵巢癌。不同模型系统中的观察表明这两种途径之间存在复杂且动态的串扰。在脊椎动物的早期发育过程中，FAK 蛋白是正确调节 Wnt/β-连环蛋白信号传导所必需的，从而控制发育中的神经系统的模式形成。在非洲爪蟾胚胎中，FAK 蛋白缺失消除了神经板中 Wnt3a 基因的表达。在小鼠破骨细胞中，通过 FAK 激活进行机械刺激可稳定 β-连环蛋白，从而促进其核转位。相比之下，在小鼠肠道中，FAK 活性在 Wnt 下游被诱导，以促进肠道再生，并且对于结直肠癌 APC 缺失模型中的肿瘤发生也至关重要。更复杂的是，在人类细胞系中，FAK 诱导 Wnt 信号传导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 通路过度激活有关。 FAK 和 Wnt 通路活性的增加独立地与特发性肺纤维化 (IPF) 有关，这是一种病因不明的肺部疾病。揭示 IPF 中的 FAK-Wnt 连接可以提供对疾病病理学的更好理解。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 通路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。
Recent studies connect the FAK and Wnt/beta-catenin signaling pathways, both which promote cancer when aberrantly activated in mammalian cells. Over-stimulation of either Wnt/beta-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/beta-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 beta-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/beta-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.