We observed that reduced intestinal JAK3 expression during human obesity or JAK3 knockout in mouse or siRNA-mediated β-catenin knockdown in human intestinal epithelial cells all result in significant loss of intestinal BCRP expression and compromised colonic drug efflux and barrier functions.
Obesity and nuclear β-catenin are independent favorable prognostic factors for DFS in locally advanced cancer treated with preoperative radiochemotherapy.J. Surg.Oncol.2017;115:301-306.
In addition to known driver mutations in TP53 and CTNNB1, our mutation analysis identified non-synonymous mutations in genes implicated in metabolic diseases, i.e. diabetes and obesity: IRS1, HMGCS1, ATP8B1, PRMT6 and CLU, suggesting a common molecular etiology for HCC of alternative pathogenic origin.
Our results reveal a mechanism by which high glucose enhances signaling through the cancer-associated Wnt/β-catenin pathway and may explain the increased frequency of cancer associated with obesity and diabetes.