Hiremath Ishita S, Goel Arul, Warrier Sudha, Kumar Alan Prem, Sethi Gautam, Garg Manoj
Department of Bioengineering, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
La Canada High School, La Canada Flintridge, California, USA.
J Cell Physiol. 2022 Jan;237(1):199-238. doi: 10.1002/jcp.30561. Epub 2021 Aug 25.
Several signaling pathways have been identified as important for developmental processes. One of such important cascades is the Wnt/β-catenin signaling pathway, which can regulate various physiological processes such as embryonic development, tissue homeostasis, and tissue regeneration; while its dysregulation is implicated in several pathological conditions especially cancers. Interestingly, deregulation of the Wnt/β-catenin pathway has been reported to be closely associated with initiation, progression, metastasis, maintenance of cancer stem cells, and drug resistance in human malignancies. Moreover, several genetic and experimental models support the inhibition of the Wnt/β-catenin pathway to answer the key issues related to cancer development. The present review focuses on different regulators of Wnt pathway and how distinct mutations, deletion, and amplification in these regulators could possibly play an essential role in the development of several cancers such as colorectal, melanoma, breast, lung, and leukemia. Additionally, we also provide insights on diverse classes of inhibitors of the Wnt/β-catenin pathway, which are currently in preclinical and clinical trial against different cancers.
几种信号通路已被确定对发育过程至关重要。其中一个重要的级联反应是Wnt/β-连环蛋白信号通路,它可以调节各种生理过程,如胚胎发育、组织稳态和组织再生;而其失调与多种病理状况尤其是癌症有关。有趣的是,据报道Wnt/β-连环蛋白通路的失调与人类恶性肿瘤的起始、进展、转移、癌症干细胞的维持以及耐药性密切相关。此外,一些遗传和实验模型支持抑制Wnt/β-连环蛋白通路以解决与癌症发展相关的关键问题。本综述重点关注Wnt通路的不同调节因子,以及这些调节因子中不同的突变、缺失和扩增如何可能在几种癌症(如结直肠癌、黑色素瘤、乳腺癌、肺癌和白血病)的发展中发挥重要作用。此外,我们还提供了关于Wnt/β-连环蛋白通路不同类型抑制剂的见解,这些抑制剂目前正处于针对不同癌症的临床前和临床试验阶段。