| First Author | Lu TL | Year | 2015 |
| Journal | J Pathol | Volume | 236 |
| Issue | 3 | Pages | 290-301 |
| PubMed ID | 25712462 | Mgi Jnum | J:222750 |
| Mgi Id | MGI:5645455 | Doi | 10.1002/path.4521 |
| Citation | Lu TL, et al. (2015) Differential requirements for beta-catenin in murine prostate cancer originating from basal versus luminal cells. J Pathol 236(3):290-301 |
| abstractText | A driver mutation occurring in different cells of origin may impact cancer progression differently. Previously, we demonstrated higher invasiveness in Pten-deficient prostate cancer (CaP) arising from basal cells compared to that arising from luminal cells in mice. Here, we show higher expression of epithelial-mesenchymal transition (EMT)-inducing transcription factors and stem/progenitor properties in basal-derived CaP compared to luminal-derived CaP. We further explore the requirement for beta-catenin in basal and luminal prostate cells during CaP progression. Genetic ablation and pharmacological inhibition of beta-catenin specifically suppress basal-derived CaP progression through reduction of stemness and cell proliferation and increased gammaH2Ax-associated apoptosis. Lineage tracing revealed that loss of beta-catenin in basal cells impairs basal-to-luminal differentiation; conversely, beta-catenin loss is dispensable for luminal-derived CaP progression. Our findings suggest that beta-catenin is required for basal-derived normal luminal cells and cancer cells, but not for luminal derivatives. Although the cellular origin of CaP in patients cannot be easily determined at present, the results imply that beta-catenin inhibition is a potential therapeutic option for a subset of patients with basal-derived CaP. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
