Arsenic promotes the COX2/PGE2-SOX2 axis to increase the malignant stemness properties of urothelial cells.

ABSTRACT: Chronic arsenic exposure is associated with the development of urothelial carcinoma of the bladder (UCB). To elucidate the contribution of arsenic exposure to urothelial cancer stem cell (CSC) generation, we established an in vitro stepwise malignant model transformed by chronically exposing human urothelial cells to arsenic. Using this model, we found that chronic arsenic exposure endows urothelial cells with malignant stemness properties including increased expression of stemness-related factors such as SOX2, sphere formation, self-renewal, invasion and chemoresistance. SOX2 was gradually and irreversibly overexpressed in line with acquired sphere-forming and self-renewal abilities. Following gene set enrichment analyses of arsenic-exposed and arsenic-unexposed cells, we found COX2 as an

SUBMITTER: Ooki A 

PROVIDER: S-EPMC5938132 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature