RRC ID 32720
Author Lu TL, Chen CM.
Title Differential requirements for β-catenin in murine prostate cancer originating from basal versus luminal cells.
Journal J Pathol
Abstract 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 β-catenin in basal and luminal prostate cells during CaP progression. Genetic ablation and pharmacological inhibition of β-catenin specifically suppress basal-derived CaP progression through reduction of stemness and cell proliferation and increased γH2Ax-associated apoptosis. Lineage tracing revealed that loss of β-catenin in basal cells impairs basal-to-luminal differentiation; conversely, β-catenin loss is dispensable for luminal-derived CaP progression. Our findings suggest that β-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 β-catenin inhibition is a potential therapeutic option for a subset of patients with basal-derived CaP.
Volume 236(3)
Pages 290-301
Published 2015-7-1
DOI 10.1002/path.4521
PMID 25712462
MeSH Animals Cell Differentiation Cell Lineage Cell Proliferation Disease Progression Epithelial Cells / metabolism Epithelial Cells / pathology Epithelial-Mesenchymal Transition Humans Male Mice Mutation PTEN Phosphohydrolase / deficiency PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism* Prostatic Neoplasms / genetics Prostatic Neoplasms / metabolism* Prostatic Neoplasms / pathology Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism beta Catenin / metabolism*
IF 6.021
Times Cited 10
Mice RBRC02228