A Nucleotide Analog Prevents Colitis-Associated Cancer via Beta-Catenin Independently of Inflammation and Autophagy
Yong Hua Sheng, Rabina Giri, Julie Davies, Veronika Schreiber, Saleh Alabbas, Ramya Movva, Yaowu He, Andy Wu, John Hooper, Brett McWhinney, Iulia Oancea, Gregor Kijanka, Sumaira Hasnain, Andrew J Lucke, David P Fairlie, Michael A McGuckin, Timothy H Florin, Jakob Begun
Cellular and Molecular Gastroenterology and Hepatology | ELSEVIER INC | Published : 2021
BACKGROUND & AIMS: Chronic bowel inflammation increases the risk of colon cancer; colitis-associated cancer (CAC). Thiopurine treatments are associated with a reduction in dysplasia and CAC in inflammatory bowel disease (IBD). Abnormal Wnt/β-catenin signalling is characteristic of >90% of colorectal cancers. Immunosuppression by thiopurines is via Rac1 GTPase, which also affects Wnt/β-catenin signalling. Autophagy is implicated in colonic tumors, and topical delivery of the thiopurine thioguanine (TG) is known to alleviate colitis and augment autophagy. This study investigated the effects of TG in a murine model of CAC and potential mechanisms. METHODS: Colonic dysplasia was induced by expos..View full abstract
The Translational Research Institute (TRI) is supported by a grant from the Australian Government. Mater Research Institute is supported by Mater Foundation. JB has a UQ Reginald Ferguson Fellowship. AJL is supported by an ARC grant and DPF by the NHMRC.