Abstract

Gastric cancer is the second leading cause of cancer-related deaths worldwide. Gastric cancer is often detected at a late stage when treatment is difficult. Biomarkers for early detection and drug targets for gastric cancer therapy are critical for effective management of gastric cancer. Secreted proteins not only play integral roles in cancer progression and metastasis, they are also easily accessible. Secreted proteins within the tumor microenvironment are therefore an attractive source of biomarkers and drug targets. In this study, iTRAQ-based liquid chromatography/tandem mass spectrometry was used for comparative profiling of the secretomes of 11 gastric cancer cell lines versus a normal gastric epithelial cell line. Of the close to 800 proteins detected, about 600 proteins were detected to display differential expression in one or more gastric cancer cell lines compared to normal cells. These differentially expressed proteins predominantly have binding or enzymatic activities and are largely associated with cellular and metabolic processes. Overexpression of ARPC4 was validated in gastric cell lines and its novel function in gastric cancer cell migration and invasion demonstrated in vitro. The findings support the notion of ARPC4 as a potential biomarker/drug target for metastatic gastric cancer.

Keywords: ARPC4, gastric cancer, secretomes, migration, invasion.

Graphical Abstract