MUC13 promotes the development of colitis-associated colorectal tumors via beta-catenin activity
Yong Hua Sheng, Kuan Yau Wong, Inge Seim, Ran Wang, Yaowu He, Andy Wu, Maya Patrick, Rohan Lourie, Veronika Schreiber, Rabina Giri, Choa Ping Ng, Amirali Popat, John Hooper, Gregor Kijanka, Timothy H Florin, Jakob Begun, Kristen J Radford, Sumaira Hasnain, Michael A McGuckin
Oncogene | NATURE PUBLISHING GROUP | Published : 2019
Many adenocarcinomas, including colorectal cancer (CRC), overexpress the MUC13 cell surface mucin, but the functional significance and mechanisms are unknown. Here, we report the roles of MUC13 in colonic tumorigenesis and tumor progression. High-MUC13 expression is associated with poor survival in two independent patient cohorts. In a comprehensive series of in vivo experiments, we identified a critical role for MUC13 in the development of this malignancy, by promoting survival and proliferation of tumor-initiating cells and driving an immunosuppressive environment that protects tumors from checkpoint inhibitor immunotherapy. In Muc13-deficient mice, fewer tumors are generated after exposur..View full abstract
Awarded by NHMRC
Supported by NHMRC project grant 1060698 and funding by the Mater Foundation, MAM was supported by an NHMRC Principal Research Fellowship. RL was partly supported by a Betty McGrath/Mater Practitioner Research Fellowship. IS is supported by a QUT Vice-Chancellor's Senior Research Fellowship. The Translational Research Institute (TRI) is supported by a grant from the Australian Government.