Selvam S, Vairappan B. Tight junction proteins: Gatekeepers turned facilitators in the pathogenesis of gastric adenocarcinoma. World J Gastrointest Oncol 2026; 18(1): 114040 [PMID: 41607753 DOI: 10.4251/wjgo.v18.i1.114040]
Corresponding Author of This Article
Balasubramaniyan Vairappan, PhD, Additional Professor, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Pondicherry 605006, India. balasubramaniyan.v@jipmer.edu.in
Research Domain of This Article
Gastroenterology & Hepatology
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. Jan 15, 2026; 18(1): 114040 Published online Jan 15, 2026. doi: 10.4251/wjgo.v18.i1.114040
Tight junction proteins: Gatekeepers turned facilitators in the pathogenesis of gastric adenocarcinoma
Shobha Selvam, Balasubramaniyan Vairappan
Shobha Selvam, Balasubramaniyan Vairappan, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India
Co-first authors: Shobha Selvam and Balasubramaniyan Vairappan.
Author contributions: Selvam S and Vairappan B contributed equally to this manuscript and are co-first authors. Selvam S and Vairappan B contributed to the manuscript writing and revisions.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Balasubramaniyan Vairappan, PhD, Additional Professor, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantari Nagar, Pondicherry 605006, India. balasubramaniyan.v@jipmer.edu.in
Received: September 10, 2025 Revised: October 21, 2025 Accepted: November 24, 2025 Published online: January 15, 2026 Processing time: 124 Days and 18 Hours
Abstract
Gastric cancer (GC) is the fifth most prevalent malignancy worldwide and remains a leading cause of cancer-related mortality. Major risk factors for GC include Helicobacter pylori infection, increasing age, high dietary salt intake, and diets deficient in vegetables and fruits. Due to the often subtle and nonspecific early symptoms, coupled with the lack of routine screening programs, a significant proportion of GC cases are diagnosed at advanced stages. The etiology of GC is multifactorial, and diagnosis is confirmed histologically through endoscopic biopsy, followed by staging via computed tomography, positron emission tomography, staging laparoscopy, and endoscopic ultrasound. Treatment strategies typically involve a multidisciplinary approach including chemotherapy, surgical resection, radiotherapy, and emerging immunotherapeutic options. Despite advances in diagnostic and therapeutic modalities, the prognosis of advanced GC remains poor, with high rates of recurrence and metastasis. In recent years, increasing attention has been given to the role of tight junction (TJ) proteins in the pathogenesis and progression of GC. TJ proteins, critical components of epithelial barrier function, have been implicated in various stages of gastric carcinogenesis, from intestinal metaplasia to invasion and metastasis. Infection and inflammation, particularly due to Helicobacter pylori, disrupt TJ integrity, compromising the gastric mucosal barrier and facilitating neoplastic transformation. This review synthesizes current evidence from PubMed, EMBASE, Google Scholar, ScienceDirect, SpringerLink, and other reputable databases to provide a comprehensive overview of the involvement of TJ proteins in GC. By elucidating the molecular interplay between TJ dysregulation and gastric tumorigenesis, this work aims to highlight the potential of TJ proteins as novel diagnostic biomarkers and therapeutic targets in GC management.
Core Tip: Tight junction (TJ) proteins play a pivotal role in preserving the integrity of the gastric epithelial barrier. Their dysregulation represents a critical early event linking chronic inflammation to gastric carcinogenesis. Inflammatory mediators induce TJ remodeling, thereby increasing mucosal permeability and promoting tumor initiation and progression. Emerging therapeutic strategies targeting TJ proteins either by pharmacologically restoring barrier integrity or modulating aberrant TJ signaling offer promising avenues to suppress inflammation, inhibit tumor growth and metastasis, and ultimately improve clinical outcomes in gastric cancer patients.
