Wen JK, Xia J, Yu L, Xu GL, Ye GF, Lin YH. Could deciphering cellular-mesenchymal epithelial transition factor/hepatocyte growth factor network dynamics unlock novel biomarker-driven therapies for colorectal cancer? World J Gastrointest Oncol 2026; 18(4): 114567 [DOI: 10.4251/wjgo.v18.i4.114567]
Corresponding Author of This Article
Yu-Hua Lin, PhD, Department of Respiratory Medicine, Xiamen TCM Hospital Affiliated to Fujian University of Traditional Chinese Medicine, No. 1739 Xianyue Road, Xiamen 361015, Fujian Province, China. lin1083885768@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Apr 15, 2026; 18(4): 114567 Published online Apr 15, 2026. doi: 10.4251/wjgo.v18.i4.114567
Could deciphering cellular-mesenchymal epithelial transition factor/hepatocyte growth factor network dynamics unlock novel biomarker-driven therapies for colorectal cancer?
Jun-Kai Wen, Jing Xia, Lu Yu, Guo-Liang Xu, Gang-Fu Ye, Yu-Hua Lin
Jun-Kai Wen, Lu Yu, Guo-Liang Xu, Gang-Fu Ye, Yu-Hua Lin, Department of Respiratory Medicine, Xiamen TCM Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Xiamen 361015, Fujian Province, China
Jing Xia, Department of Traditional Chinese Medicine, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou 350002, Fujian Province, China
Co-first authors: Jun-Kai Wen and Jing Xia.
Co-corresponding authors: Gang-Fu Ye and Yu-Hua Lin.
Author contributions: Wen JK, Xia J, and Yu L contributed to collected relevant data; Wen JK and Xia J contributed equally to this manuscript as co-first authors; Xia J contributed to prepared the figures; Wen JK and Yu L contributed to drafted the manuscript; Xu GL, Ye GF, and Lin YH contributed to conceived the review, provided methodological guidance, and revised the manuscript critically; Ye GF and Lin YH contributed equally to this manuscript as co-corresponding authors; and all authors have read and approved the final manuscript.
Supported by Xiamen Health Commission High-Quality Development Science and Technology Plan Project, No. 2024GZL-GG49; Fujian Province Natural Science Foundation Project, No. 2024J08328; Fujian Provincial Health Commission Youth Research Project, No. 2024QNB021; and National Natural Science Foundation of China (Youth) Program, No. 82405349.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Yu-Hua Lin, PhD, Department of Respiratory Medicine, Xiamen TCM Hospital Affiliated to Fujian University of Traditional Chinese Medicine, No. 1739 Xianyue Road, Xiamen 361015, Fujian Province, China. lin1083885768@163.com
Received: September 23, 2025 Revised: December 1, 2025 Accepted: January 14, 2026 Published online: April 15, 2026 Processing time: 197 Days and 16 Hours
Abstract
Colorectal cancer (CRC) poses a substantial global health challenge. Its pathogenesis involves intricate genetic and signaling pathway aberrations, among which the cellular-mesenchymal epithelial transition factor (c-Met)/hepatocyte growth factor (HGF) axis functions as a pivotal regulatory hub. Encoded by a proto-oncogene, the transmembrane receptor c-Met is activated by HGF, driving CRC cell proliferation, migration, invasion, and metastasis via critical signal transduction cascades. The c-Met factor overexpression is observed in 30%-70% of CRC tumors. This review elucidates c-Met/HGF-mediated carcinogenesis, emphasizing its crosstalk with epidermal growth factor receptor, vascular endothelial growth factor, and insulin-like growth factor 1 receptor pathways. Notably, c-Met amplification contributes to epidermal growth factor receptor inhibitor resistance, increasing signaling network complexity. MicroRNA-1 and microRNA-137 modulate c-Met expression to suppress CRC progression, while advancements in c-Met-targeted molecular imaging facilitate precise diagnosis and treatment monitoring. Progress in c-Met/HGF-targeted therapies, including small-molecule inhibitors, monoclonal antibodies, and tyrosine kinase inhibitors, shows promise in suppressing tumors and overcoming resistance. Future efforts should focus on optimizing combination therapies, refining patient stratification via imaging, and addressing drug resistance to enable personalized, efficacious CRC treatments leveraging this axis.
Core Tip: This comprehensive review delineates the complex cellular-mesenchymal epithelial transition factor (c-Met)/hepatocyte growth factor signaling network as a central driver of colorectal cancer progression, metastasis, and resistance to epidermal growth factor receptor-targeted therapies. We highlight innovative insights, including the distinct tumor-suppressive roles of microRNA-1 and microRNA-137 in regulating c-Met, the critical function of the transcriptional activator metastasis associated in colon cancer 1, and the pathway’s extensive crosstalk with vascular endothelial growth factor and insulin-like growth factor-1 receptor. The review synthesizes recent advances in c-Met-targeted agents (inhibitors and monoclonal antibodies) and emerging non-invasive molecular imaging techniques. It proposes novel, biomarker-driven combination strategies and patient stratification approaches to overcome therapeutic resistance, paving the way for personalized treatment in colorectal cancer.
