Function and mechanism of exogenous AGR2 in colorectal cancer cells

Abstract

BackgroundAnterior gradient 2 (AGR2) is highly enriched in several malignant tumors and can boost tumor metastasis. Whereas, AGR2 role in colorectal cancer (CRC) is not clear. MethodsAGR2 expression in the GEPIA database was studied, and the results were confirmed by Western blot in CRC cell lines (SW480, SW620, and HT-29). The impact of AGR2 on the multiplication, migration, invasion and EMT of CRC cells were studied by CCK-8 assay, as well as clone formation, wound healing and transwell assays. The protein concent related to the AKT/β-catenin signaling pathway were accessed via Western blot. ResultsAGR2 concent in CRC tissues was notablely boosted versus normal colorectal tissues. Exogenous AGR2 boosted the multiplication of CRC cells. In addition, exogenous AGR2 induced EMT, which demonstrated that ZEB1, N-cadherin, Vimentin, Slug, Snail protein concent boosted and E-cadherin protein abated in CRC cells. In terms of mechanism, exogenous AGR2 upgulated p-AKT/AKT, p-GSK3β/GSK3β and β-catenin concent. Exogenous AGR2 combined with AKT agonist IGF- Ⅰ can further enhance the multiplication, migration and invasion of CRC cells. ConclusionExogenous AGR2 enhances the multiplication of CRC cells and induces EMT process, the mechanism of which is related to AKT/β-catenin signal pathway.