Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Apr 26, 2022; 10(12): 3647-3661
Published online Apr 26, 2022. doi: 10.12998/wjcc.v10.i12.3647
Role of zonula occludens in gastrointestinal and liver cancers
Amit Kumar Ram, Balasubramaniyan Vairappan
Amit Kumar Ram, Balasubramaniyan Vairappan, Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India
Author contributions: Ram AK wrote the manuscript; Vairappan B critically reviewed the manuscript.
Supported by JIPMER intramural research grant, Indian Council of Medical Research (ICMR), New Delhi, India, No. 3/1/3 J.R.F.-2016/LS/HRD.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
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, Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Pondicherry 605006, India. balasubramaniyan.v@jipmer.edu.in
Received: May 10, 2021
Peer-review started: May 20, 2021
First decision: July 16, 2021
Revised: August 8, 2021
Accepted: March 4, 2022
Article in press: March 4, 2022
Published online: April 26, 2022
Processing time: 345 Days and 20.2 Hours
Abstract

A growing body of evidence suggests that tight junction (TJ) proteins play a crucial role in the pathogenesis of various diseases, including gastrointestinal (GI) cancer and hepatocellular carcinoma (HCC). TJ proteins primarily maintain the epithelial and endothelial cells intact together through integral proteins however, recent reports suggest that they also regulate gene expression necessary for cell proliferation, angiogenesis, and metastasis through adapter proteins such as zonula occludens (ZO). ZO proteins are membrane-associated cytosolic scaffolding proteins that modulate cell proliferation by interacting with several transcription factors. Reduced ZO proteins in GI cancer and HCC are correlated with tumor development and poor prognosis. Pubmed has searched for using the keyword ZO and gastric cancer, ZO and cancer, and ZO and HCC for the last ten years to date. This review summarized the role of ZO proteins in cell proliferation and their expression in GI cancer and HCC. Furthermore, therapeutic interventions targeting ZO in GI and liver cancers are reviewed.

Keywords: Tight junction; Zonula occludens-1; Zonula occludens-1 associated nucleic acid binding protein; Hepatocellular carcinoma; Colon cancer; Gastric cancer

Core Tip: Zonula occludens (ZO) proteins (ZO-1, -2, -3) are primarily involved in tight junction formation. Additionally, ZO proteins regulate cell proliferation by interacting with various transcription factors, among which ZO/ZO-1 associated nucleic acid-binding protein pathway is of particular importance. Reduced expression of ZO proteins is correlated with poor prognosis in gastrointestinal cancer and hepatocellular carcinoma. Modulating ZO proteins expression with polyphenols, probiotics and peptides may represent promising therapeutic agents for cancer treatment.