Biology

Dr. Rachana Patel
The Beatson Institute for Cancer Research, Scotland

Abstract:

Androgen receptor (AR) antagonism is a major strategy to treat advanced prostate cancers. Despite the prevalence of ß-catenin mutations in many cancer types, genomic alterations in ß-catenin are associated with treatment-resistance only in prostate cancer. Here, we have investigated the relevance of ß-catenin activating mutation in prostate cancer progression. We find that ß-catenin activation decreases Pten expression and, independent of the cell-of-origin, ß-catenin activation and Pten haploinsufficiency cooperate to mediate AR-deficient metastatic castration-resistant prostate cancer. ß-catenin mutant prostate tumours rely on WNT5a, a non-canonical WNT ligand for sustained growth. Overall, WNT/ß-catenin and AR signalling are reciprocally inhibited. Therefore, inhibiting WNT/ß-catenin signalling by limiting WNT secretion along with AR inhibition may be useful in treating prostate cancers with ß-catenin mutations.