Abstract:

Gastric cancer is the second leading cause of cancer-related death in China. Gastric adenocarcinoma comprises 95% of the total number of gastric malignancies which is often insensitive to chemo- and radiation therapy, and the 5-year survival rate of patients is only 15%-20%. Therefore, majority of studies have focused on early diagnosis and targeted therapy of gastric cancer. Our studies have found that human anion exchanger 1 (AE1), an erythrocyte membrane protein, is unexpectedly expressed in the gastric cancer with 83% frequency. Failure in negative feedback regulation between p65 and miR-24 is involved in aberrant expression of AE1. AE1 is accumulated in cytoplasm because the gastric epithelial cells do not have the ability for AE1 membrane trafficking. The cytoplasmic AE1 takes part in the gastric carcinogenesis through several signal pathways which communicate with each other: ①AE1 interacts with the tumor suppressor p16 and sequesters it in the cytoplasm, which leads to loss of negative cell cycle regulation. ②AE1 interrupts AE2 to traffick to the plasma membrane, resulting in intracellular alkalization and activation of Wnt/β-catenin pathway in gastric epithelium. The results have been included in Atlas of Genetics and Cytogenetics in Oncology and Haematology. Based on the premise that AE1 is a useful biomarker for gastric cancer, the AE1-targeted gastric cancer therapy has been carried out. The results showed that targeting of AE1 significantly inhibited the growth of gastric cancer cells. In drug-induced mouse gastric cancer model, the detection rate for gastric cancer was decreased from 62%-70% to 15.8% after knockdown of AE1. AE1 protein, as a target, has important value in diagnosis and treatment of gastric cancer.

Key words: band 3 protein, anion exchanger 1, gastric cancer, targeted therapy