Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 105264
Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.105264
Nav1.6 drives colorectal cancer proliferation and invasion through MAPK signaling pathway
Li-Ming Zhao, Wan-Ying Hong, Jian-Guang Xu, Shui-Quan Lin, Ming-Sheng Liu, Li-Hui Wang, Xu-Li Jiang, Ming Sang, Yang-Bo Lv
Li-Ming Zhao, Wan-Ying Hong, Jian-Guang Xu, Department of Gastroenterology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324002, Zhejiang Province, China
Shui-Quan Lin, Ming-Sheng Liu, Li-Hui Wang, Xu-Li Jiang, Yang-Bo Lv, Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324002, Zhejiang Province, China
Ming Sang, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu Province, China
Co-first authors: Li-Ming Zhao and Wan-Ying Hong.
Co-corresponding authors: Ming Sang and Yang-Bo Lv.
Author contributions: Hong WY and Xu JG screened patients and clinical sample collection; Lin SQ and Liu MS performed initial screening of microarray datasets, single-cell sequencing data analysis and weighted gene co-expression network analysis; Wang LH performed immunohistochemistry and immunofluorescence; Jiang XL performed cell culture and transfection, quantitative RT-PCR assay and western blots; Zhao LM and Hong WY performed Transwell assay, wound healing assays and cell counting kit-8 assay; Both Lv YB and Sang M have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors; Lv YB applied for and obtained the funds for this research project; Lv YB conceptualized, designed, and supervised the whole process of the project. He searched the literature, revised and submitted the early version of the manuscript and submission of the current version of the manuscript with the focus on Nav1.6 is overexpressed in CRC tissues and is positively correlated with tumor progression. Sang M was instrumental and responsible for data re-analysis and re-interpretation, figure plotting, comprehensive literature search and preparation with a new focus on Nav1.6 contributes to CRC metastasis and on potential underlying mechanisms. This collaboration between Lv YB and Sang M is crucial for the publication of this manuscript and other manuscripts still in preparation. All authors have read and agreed to the published version of the manuscript.
Supported by Science and Technology Project of Quzhou of China, No. 2021Y011; and Beijing Science and Technology Innovation Medical Development Foundation, No. KC2021-JX-0186-81.
Institutional review board statement: All experimental steps of this experiment have been approved by the medical ethics committee of Quzhou people's Hospital (approved number SWYX: No. 2022-034).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The study data are available from the corresponding author or any co-author upon request at lyb20110115@163.com.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yang-Bo Lv, Department of Colorectal Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, No. 100 Minjiang Avenue, Quzhou 324002, Zhejiang Province, China. lyb20110115@163.com
Received: January 18, 2025
Revised: March 12, 2025
Accepted: April 21, 2025
Published online: July 15, 2025
Processing time: 179 Days and 6.3 Hours
Core Tip

Core Tip: Voltage-gated sodium channels are prominently expressed in various tumors and play a crucial role in tumor metastasis and invasion. Our research identified 575 differentially expressed genes related to Nav1.6 in colorectal cancer (CRC), particularly enriched in MAPK signaling pathways. Tissue microarray revealed heightened Nav1.6 levels in CRC tissues. The cytoplasmic expression of Nav1.6 increases with T staging. Knockdown of SCN8A in colon tumor cells significantly decreased cell proliferation and invasion, along with downregulation of key proteins in the RAF-MAPK pathway. These findings suggest that Nav1.6 enhances CRC cell proliferation and invasion through modulation of the MAPK signaling pathway.