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Differential requirements for β‐catenin in murine prostate cancer originating from basal versus luminal cells
Author(s) -
Lu TsaiLing,
Chen ChunMing
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4521
Subject(s) - prostate cancer , basal (medicine) , differential (mechanical device) , prostate , biology , catenin , cancer research , pathology , cancer , medicine , microbiology and biotechnology , endocrinology , wnt signaling pathway , physics , signal transduction , insulin , thermodynamics
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 γ H2Ax ‐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 . Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.