Unraveling the Hippo pathway: YAP/TAZ as central players in cancer metastasis and drug resistance.

IF 4.9 3区 生物学 Q1 BIOLOGY
EXCLI Journal Pub Date : 2025-06-06 eCollection Date: 2025-01-01 DOI:10.17179/excli2025-8351
Nehmat Ghaboura
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Abstract

In regulating cellular plasticity, epithelial to mesenchymal transition (EMT), and tumor progression across a broad range of cancer types, the Hippo signaling pathway depends on YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ binding motif) as core effectors. This pathway can become dysregulated, disrupting tissue homeostasis and promoting oncogenic processes such as metastasis, immune evasion, and therapy resistance. This review explores the multifaceted roles of YAP/TAZ in lung, breast, ovarian, liver, and renal cancers, detailing their interactions with key signaling pathways such as TGF-β, Wnt, and PI3K/AKT and their modulation by mechanical cues like extracellular matrix stiffness and fluid shear stress. Potential YAP/TAZ mediated therapy resistance in EGFR TKI-resistant lung cancer and platinum-resistant ovarian cancer and the impact this has on tumor metabolism as a result of YAP/TAZ controlling tumor mesenchymal stem cells in the hypoxic environment of hepatocellular carcinoma is highlighted. Additionally, we discuss their role in maintaining cancer stem cell traits, creating an immunosuppressive tumor microenvironment, and driving chemoresistance in breast and renal cancers. Small molecule inhibitors, natural compounds (luteolin, apigenin, honokiol), and novel agents (nanoparticles of zinc oxide) are discussed as promising routes for disrupting YAP/TAZ. The review underscores the complexity of YAP/TAZ signaling and the need for patient stratification based on their expression levels to optimize targeted therapies. See also the graphical abstract(Fig. 1).

揭示Hippo通路:YAP/TAZ在癌症转移和耐药中的核心作用。
在调节细胞可塑性、上皮向间质转化(EMT)和多种癌症类型的肿瘤进展中,Hippo信号通路依赖于YAP (yes相关蛋白)和TAZ(带PDZ结合基序的转录共激活因子)作为核心效应物。该通路可能失调,破坏组织稳态,促进肿瘤发生过程,如转移、免疫逃避和治疗抵抗。这篇综述探讨了YAP/TAZ在肺癌、乳腺癌、卵巢癌、肝癌和肾癌中的多方面作用,详细介绍了它们与TGF-β、Wnt和PI3K/AKT等关键信号通路的相互作用,以及细胞外基质刚度和流体剪切应力等机械信号对它们的调节。在EGFR tki耐药肺癌和铂耐药卵巢癌中潜在的YAP/TAZ介导的治疗耐药,以及由于YAP/TAZ在肝细胞癌缺氧环境中控制肿瘤间充质干细胞而对肿瘤代谢的影响。此外,我们还讨论了它们在维持癌症干细胞特性、创造免疫抑制肿瘤微环境和驱动乳腺癌和肾癌化疗耐药中的作用。小分子抑制剂、天然化合物(木贼素、芹菜素、厚朴酚)和新型试剂(氧化锌纳米颗粒)被认为是破坏YAP/TAZ的有希望的途径。该综述强调了YAP/TAZ信号的复杂性,以及基于其表达水平对患者进行分层以优化靶向治疗的必要性。另见图解摘要(图1)。1).
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
EXCLI Journal
EXCLI Journal BIOLOGY-
CiteScore
8.00
自引率
2.20%
发文量
65
审稿时长
6-12 weeks
期刊介绍: EXCLI Journal publishes original research reports, authoritative reviews and case reports of experimental and clinical sciences. The journal is particularly keen to keep a broad view of science and technology, and therefore welcomes papers which bridge disciplines and may not suit the narrow specialism of other journals. Although the general emphasis is on biological sciences, studies from the following fields are explicitly encouraged (alphabetical order): aging research, behavioral sciences, biochemistry, cell biology, chemistry including analytical chemistry, clinical and preclinical studies, drug development, environmental health, ergonomics, forensic medicine, genetics, hepatology and gastroenterology, immunology, neurosciences, occupational medicine, oncology and cancer research, pharmacology, proteomics, psychiatric research, psychology, systems biology, toxicology
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