Role of zonula occludens in gastrointestinal and liver cancers

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.

Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p

“…TJ proteins, through integral proteins, maintain the intactness of epithelial and endothelial cells. They can also regulate the expression of various genes essential for the spread of cancer cells through adapter proteins such as zonula occludens (ZO) [51]. The increase in ZO levels decreased HepG2 cell growth by trapping the cells in the G1 phase of the cell cycle [52].…”

“…TJ proteins, through integral proteins, maintain the intactness of epithelial and endothelial cells. They can also regulate the expression of various genes essential for the spread of cancer cells through adapter proteins such as zonula occludens (ZO) [51]. The increase in ZO levels decreased HepG2 cell growth by trapping the cells in the G1 The family of Ras oncogenes stimulates the initiation of tumor growth and angiogenesis, where the oncogenic H-and K-Ras stimulate VEGF synthesis and subsequently promote tumor vascularization and development [62].…”

Tight Junction Proteins as Therapeutic Targets to Treat Liver Fibrosis and Hepatocellular Carcinoma

“…However, no enrolled patient had liver cancer. 104 While data on small molecule inhibitor mediated targeting of ZO protein is yet restricted to gastrointestinal cancers other than HCC (for a review see 105 ), reduction of proliferation and migration of liver cancer cells upon transgenic ZO-1 overexpression may catalyze further research on ZO-targeting therapies in HCC.…”

Cracking the intestinal lymphatic system window utilizing oral delivery vehicles for precise therapy

“…TJs are complex networks that are produced by multiprotein junctional complexes [ 83 ]. These complexes are composed of junctional adhesion molecules, regulatory proteins, and peripheral membrane proteins like zonula occludens (ZO-1 and ZO-2) as well as transmembrane integral proteins like claudins [ 84 – 88 ].…”