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WNT信号通路的进化保守性及其对癌症的影响

Evolutionary conservation and cancer implications of the WNT signaling pathway.

作者信息

Prajapati Devesh, Ambere Gayatri, Mathure Dyandevi, Karati Dipanjan, Kumar Dileep

机构信息

Department of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Poona College of Pharmacy, Pune, India.

Department of Pharmacy, School of Pharmacy, Techno India University, West Bengal, Kolkata, 7000091, India.

出版信息

Med Oncol. 2025 Aug 20;42(10):434. doi: 10.1007/s12032-025-02950-8.

Abstract

One of the essential cellular machinations co-opted by the WNT signaling pathway, including its canonical β-Catenin and non-canonical WNT/PCP and WNT/ Ca sub-pathways, are events such as apoptosis, cancer cell metabolism, inflammation, and proliferation of cancer cells. This review article discusses, in detail, the molecular mechanism of action of the WNT signaling pathway and its components, and digression into evolutionary conservation, but focuses on WNT signaling in development and cancer biology. It also discusses WNT signaling components and the potential role in colorectal cancer (CRC) targeted therapy. The emphasis of the review is on the potential of bioactive compounds, Flavonoids, including Curcumin and Resveratrol, to block WNT signaling and present an opportunity for CRC therapy. It highlights new and existing inhibitors that modulate the WNT pathway, and describes the mechanisms and the evidence for clinical efficacy of these drugs and compounds. This review also provides a comprehensive analysis and talks about ground-breaking discoveries of WNT pathway components and their novel roles in cancer stemness, metastasis, and immune surveillance. As such, this article described the progress toward accumulating evidence of targeting the WNT pathway, describing the clinical trials targeting PORCN inhibitors, FZD antagonists, and inhibitors of β-Catenin transcriptional activity, making it a thorough search of the WNT signaling pathway in cancer that provides potential therapeutic opportunities.

摘要

WNT信号通路(包括其经典的β-连环蛋白以及非经典的WNT/PCP和WNT/Ca子通路)所采用的基本细胞机制之一,是诸如细胞凋亡、癌细胞代谢、炎症和癌细胞增殖等事件。这篇综述文章详细讨论了WNT信号通路及其组成部分的分子作用机制,并涉及进化保守性,但重点是发育和癌症生物学中的WNT信号传导。它还讨论了WNT信号传导成分以及在结直肠癌(CRC)靶向治疗中的潜在作用。该综述的重点是生物活性化合物黄酮类化合物(包括姜黄素和白藜芦醇)阻断WNT信号传导并为CRC治疗提供机会的潜力。它强调了调节WNT通路的新的和现有的抑制剂,并描述了这些药物和化合物的作用机制及临床疗效证据。本综述还进行了全面分析,并探讨了WNT通路成分的突破性发现及其在癌症干性、转移和免疫监视中的新作用。因此,本文描述了在积累靶向WNT通路证据方面取得的进展,介绍了针对PORCN抑制剂、FZD拮抗剂和β-连环蛋白转录活性抑制剂的临床试验,使其成为对癌症中WNT信号通路的全面探索,提供了潜在的治疗机会。

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