title: Differential requirements for β-catenin in murine prostate cancer originating from basal versus luminal cells.
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.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tsai-Ling
authors.initials: TL
authors.lastname: Lu
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.|VGH Genome Research Centre, National Yang-Ming University, Taipei, Taiwan.|Taiwan Mouse Clinic, National Phenotyping Centre, Taipei, Taiwan.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D051176:beta Catenin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: Pten; cell lineages; mouse model; prostate cancer