Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers.

Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers.
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DOI:
10.1053/j.gastro.2011.12.001
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发表时间:
2012-02
期刊:
影响因子:
29.4
通讯作者:
Dawson DW
Dawson DW
中科院分区:
医学1区
文献类型:
--
作者:
White BD;Chien AJ;Dawson DW

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异常Wnt/β-连环蛋白信号传导广泛涉及许多恶性肿瘤,包括胃肠道(GI)癌症。信号转导的失调传统上归因于Axin、APC(腺瘤性结肠息肉病)和β-连环蛋白的突变,其导致通路的组成性超活化。然而,Wnt/β-连环蛋白信号传导也通过癌症中的各种其他机制进行调节,包括与其他改变的信号传导途径的串扰。Wnt/β-连环蛋白信号传导及其在GI癌症中的作用的更复杂的观点现在正在出现,因为发现不同的表型结果由时空背景和相对水平的通路激活决定。本文综述了Wnt/β-catenin信号通路在结直肠癌、肝细胞癌和胰腺导管腺癌中的异常调节,特别强调了后两者。最后,我们解决了一些主要的挑战,在试图在临床上的路径为目标。
Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal (GI) tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, APC (adenomatous polyposis coli), and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including crosstalk with other altered signaling pathways. A more complex view of Wnt/β-catenin signaling and its role in GI cancers is now emerging as divergent phenotypic outcomes are found to be dictated by temporospatial context and relative levels of pathway activation. This review summarizes the dysregulation of Wnt/β-catenin signaling in colorectal carcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, with particular emphasis on the latter two. We conclude by addressing some of the major challenges faced in attempting to target the pathway in the clinic.
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