Tetraspanins: Novel Molecular Regulators of Gastric Cancer

Abstract

Gastric cancer is the fourth and fifth most common cancer worldwide in men and women, respectively. However, patients with an advanced stage of gastric cancer still have a poor prognosis and low overall survival rate. The tetraspanins belong to a protein superfamily with four hydrophobic transmembrane domains and 33 mammalian tetraspanins are ubiquitously distributed in various cells and tissues. They interact with other membrane proteins to form tetraspanin-enriched microdomains and serve a variety of functions including cell adhesion, invasion, motility, cell fusion, virus infection, and signal transduction. In this review, we summarize multiple utilities of tetraspanins in the progression of gastric cancer and the underlying molecular mechanisms. In general, the expression of TSPAN8, CD151, TSPAN1, and TSPAN4 is increased in gastric cancer tissues and enhance the proliferation and invasion of gastric cancer cells, while CD81, CD82, TSPAN5, TSPAN9, and TSPAN21 are downregulated and suppress gastric cancer cell growth. In terms of cell motility regulation, CD9, CD63 and CD82 are metastasis suppressors and the expression level is inversely associated with lymph node metastasis. We also review the clinicopathological significance of tetraspanins in gastric cancer including therapeutic targets, the development of drug resistance and prognosis prediction. Finally, we discuss the potential clinical value and current limitations of tetraspanins in gastric cancer treatments, and provide some guidance for future research.