UNBOUND

Featured here, are the extraordinary works of our graduating Fashion Design class. This accomplishment is truly a celebration of the tree years of passion, hard work, and dedication of our students. It\u27s our hope that the fashion industry will partake in the creative endeavors of the emerging designers from the Fashion Design program at Fanshawe College in London, Ontario.https://first.fanshawec.ca/famd_design_fashiondesign_unbound/1002/thumbnail.jp

BVES regulates c-Myc stability via PP2A and suppresses colitis-induced tumourigenesis

OBJECTIVE: Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumorigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function, and its relevance to inflammatory bowel disease (IBD) patients. DESIGN: We determined BVES promoter methylation status using an Infinium HumanMethylation450 array screen of patients with ulcerative colitis with and without CAC. We also measured BVES mRNA levels in a tissue microarray consisting of normal colons and CAC samples. Bves(−/−) and wild-type mice (controls) were administered azoxymethane (AOM) and dextran sodium sulfate (DSS) to induce tumor formation. Lastly, we utilized a yeast two-hybrid screen to identify BVES interactors and performed mechanistic studies in multiple cell lines to define how BVES reduces c-Myc levels. RESULTS: BVES mRNA was reduced in tumors from patients with CAC via promoter hypermethylation. Importantly, BVES promoter hypermethylation was concurrently present in distant non-malignant appearing mucosa. As seen in human patients, Bves was underexpressed in experimental inflammatory carcinogenesis, and Bves(−/−) mice had increased tumor multiplicity and degree of dysplasia after AOM/DSS administration. Molecular analysis of Bves(−/−) tumors revealed Wnt activation and increased c-Myc levels. Mechanistically, we identified a new signaling pathway whereby BVES interacts with PR61α, a PP2A regulatory subunit, to mediate c-Myc destruction. CONCLUSIONS: Loss of BVES promotes inflammatory tumorigenesis through dysregulation of Wnt signaling and the oncogene c-Myc. BVES promoter methylation status may serve as a CAC biomarker