Journal article
MUC13 promotes the development of colitis-associated colorectal tumors via β-catenin activity
YH Sheng, KY Wong, I Seim, R Wang, Y He, A Wu, M Patrick, R Lourie, V Schreiber, R Giri, CP Ng, A Popat, J Hooper, G Kijanka, TH Florin, J Begun, KJ Radford, S Hasnain, MA McGuckin
Oncogene | NATURE PUBLISHING GROUP | Published : 2019
Abstract
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..
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Awarded by American Foundation for Maternal and Child Health
Funding Acknowledgements
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.