FEST Division, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226 001, India.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
Phytomedicine. 2024 Jun;128:155379. doi: 10.1016/j.phymed.2024.155379. Epub 2024 Jan 18.
c-MET is a receptor tyrosine kinase which is classically activated by HGF to activate its downstream signaling cascades such as MAPK, PI3K/Akt/mTOR, and STAT3. The c-MET modulates cell proliferation, epithelial-mesenchymal transition (EMT), immune response, morphogenesis, apoptosis, and angiogenesis. The c-MET has been shown to serve a prominent role in embryogenesis and early development. The c-MET pathway is deregulated in a broad range of malignancies, due to overexpression of ligands or receptors, genomic amplification, and MET mutations. The link between the deregulation of c-MET signaling and tumor progression has been well-documented. Overexpression or overactivation of c-MET is associated with dismal clinical outcomes and acquired resistance to targeted therapies. Since c-MET activation results in the triggering of oncogenic pathways, abrogating the c-MET pathway is considered to be a pivotal strategy in cancer therapeutics. Herein, an analysis of role of the c-MET pathway in human cancers and its relevance in bone metastasis and therapeutic resistance has been undertaken. Also, an attempt has been made to summarize the inhibitory activity of selected natural compounds towards c-MET signaling in cancers.
The publications related to c-MET pathway in malignancies and its natural compound modulators were obtained from databases such as PubMed, Scopus, and Google Scholar and summarized based on PRISMA guidelines. Some of the keywords used for extracting relevant literature are c-MET, natural compound inhibitors of c-MET, c-MET in liver cancer, c-MET in breast cancer, c-MET in lung cancer, c-MET in pancreatic cancer, c-MET in head and neck cancer, c-MET in bone metastasis, c-MET in therapeutic resistance, and combination of c-MET inhibitors and chemotherapeutic agents. The chemical structure of natural compounds was verified in PubChem database.
The search yielded 3935 publications, of which 195 reference publications were used for our analysis. Clinical trials were referenced using ClinicalTrials.gov identifier. The c-MET pathway has been recognized as a prominent target to combat the growth, metastasis, and chemotherapeutic resistance in cancers. The key role of the c-MET in bone metastasis as well as therapeutic resistance has been elaborated. Also, suppressive effect of selected natural compounds on the c-MET pathway in clinical/preclinical studies has been discussed.
c-MET 是一种受体酪氨酸激酶，经典激活剂为 HGF，可激活其下游信号级联，如 MAPK、PI3K/Akt/mTOR 和 STAT3。c-MET 调节细胞增殖、上皮-间质转化 (EMT)、免疫反应、形态发生、细胞凋亡和血管生成。c-MET 在胚胎发生和早期发育中发挥重要作用。由于配体或受体过表达、基因组扩增和 MET 突变，c-MET 通路在广泛的恶性肿瘤中失调。c-MET 信号通路失调与肿瘤进展之间的联系已有充分的文献记载。c-MET 的过度表达或过度激活与不良的临床结局和对靶向治疗的获得性耐药有关。由于 c-MET 激活导致致癌途径的触发，因此阻断 c-MET 途径被认为是癌症治疗的关键策略。本文分析了 c-MET 通路在人类癌症中的作用及其在骨转移和治疗耐药中的相关性，并总结了一些天然化合物对癌症中 c-MET 信号的抑制活性。
从 PubMed、Scopus 和 Google Scholar 等数据库中获取与恶性肿瘤中 c-MET 通路及其天然化合物调节剂相关的出版物，并根据 PRISMA 指南进行总结。提取相关文献的一些关键词是 c-MET、c-MET 的天然化合物抑制剂、肝癌中的 c-MET、乳腺癌中的 c-MET、肺癌中的 c-MET、胰腺癌中的 c-MET、头颈部癌症中的 c-MET、骨转移中的 c-MET、治疗耐药中的 c-MET 以及 c-MET 抑制剂与化疗药物的联合。在 PubChem 数据库中验证了天然化合物的化学结构。
搜索结果产生了 3935 篇出版物，其中 195 篇参考文献用于我们的分析。临床试验使用 ClinicalTrials.gov 标识符进行参考。c-MET 通路已被认为是对抗癌症生长、转移和化疗耐药的重要靶点。详细阐述了 c-MET 在骨转移和治疗耐药中的关键作用。还讨论了一些天然化合物在临床/临床前研究中对 c-MET 通路的抑制作用。
