Dysregulation of Wnt/β‐catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application,Cancer Science

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Dysregulation of Wnt/β‐catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application
Cancer Science ( IF 4.5 ) Pub Date : 2021-02-19 , DOI: 10.1111/cas.14861
Qian Li ₁ , Mengqing Sun ₁ , Menglan Wang ₁ , Mengqing Feng ₁ , Fan Yang ₁ , Lina Li ₁ , Jianbo Zhao ₁ , Cunjie Chang ₁ , Heng Dong ₁ , Tian Xie ₁ , Jianxiang Chen _{1,

2}

Affiliation

Wnt/β‐catenin signaling is indispensable for many biological processes, including embryonic development, cell cycle, inflammation, and carcinogenesis. Aberrant activation of the Wnt/β‐catenin signaling can promote tumorigenicity and enhance metastatic potential in hepatocellular carcinoma (HCC). Targeting this pathway is a new opportunity for precise medicine for HCC. However, inhibiting Wnt/β‐catenin signaling alone is unlikely to significantly improve HCC patient outcome due to the lack of specific inhibitors and the complexity of this pathway. Combination with other therapies will be an important next step in improving the efficacy of Wnt/β‐catenin signaling inhibitors. Protein kinases play a key and evolutionarily conserved role in the Wnt/β‐catenin signaling and have become one of the most important drug targets in cancer. Targeting Wnt/β‐catenin signaling and its regulatory kinase together will be a promising HCC management strategy. In this review, we summarize the kinases that modulate the Wnt/β‐catenin signaling in HCC and briefly discuss their molecular mechanisms. Furthermore, we list some small molecules that target the kinases and may inhibit Wnt/β‐catenin signaling, to offer new perspectives for preclinical and clinical HCC studies.

中文翻译：

蛋白激酶在肝细胞癌中Wnt /β-catenin信号转导的异常及其治疗应用

Wnt /β-catenin信号对于许多生物学过程都是必不可少的，包括胚胎发育，细胞周期，炎症和癌变。Wnt /β-catenin信号的异常激活可以促进肝细胞癌（HCC）的致瘤性并增强转移潜能。靶向该途径是用于肝癌的精确药物的新机会。但是，由于缺乏特异性抑制剂和该途径的复杂性，仅抑制Wnt /β-catenin信号传导不太可能显着改善HCC患者的预后。与其他疗法的结合将是提高Wnt /β-catenin信号抑制剂功效的重要的下一步。蛋白激酶在Wnt /β-catenin信号传导中起着关键且在进化上保守的作用，已成为癌症中最重要的药物靶标之一。一起靶向Wnt /β-catenin信号及其调节激酶将是一种有前途的HCC管理策略。在这篇综述中，我们总结了调节肝癌中Wnt /β-catenin信号传导的激酶，并简要讨论了它们的分子机制。此外，我们列出了一些靶向激酶并可能抑制Wnt /β-catenin信号传导的小分子，为临床前和临床HCC研究提供了新的见解。

更新日期：2021-02-19

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