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Prostate lineage-specific metabolism governs luminal differentiation and response to antiandrogen treatment.
Giafaglione, Jenna M; Crowell, Preston D; Delcourt, Amelie M L; Hashimoto, Takao; Ha, Sung Min; Atmakuri, Aishwarya; Nunley, Nicholas M; Dang, Rachel M A; Tian, Mao; Diaz, Johnny A; Tika, Elisavet; Payne, Marie C; Burkhart, Deborah L; Li, Dapei; Navone, Nora M; Corey, Eva; Nelson, Peter S; Lin, Neil Y C; Blanpain, Cedric; Ellis, Leigh; Boutros, Paul C; Goldstein, Andrew S.
Afiliação
  • Giafaglione JM; Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
  • Crowell PD; Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA.
  • Delcourt AML; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Hashimoto T; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Ha SM; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Atmakuri A; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Nunley NM; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Dang RMA; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
  • Tian M; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
  • Diaz JA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
  • Tika E; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
  • Payne MC; Laboratory of Stem Cells and Cancer, WEL Research Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
  • Burkhart DL; Department of Mechanical & Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
  • Li D; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Navone NM; Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Corey E; Department of GU Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
  • Nelson PS; University of Washington, Seattle, WA, USA.
  • Lin NYC; Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Blanpain C; Department of Mechanical & Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
  • Ellis L; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
  • Boutros PC; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
  • Goldstein AS; Laboratory of Stem Cells and Cancer, WEL Research Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Nat Cell Biol ; 25(12): 1821-1832, 2023 Dec.
Article em En | MEDLINE | ID: mdl-38049604
ABSTRACT
Lineage transitions are a central feature of prostate development, tumourigenesis and treatment resistance. While epigenetic changes are well known to drive prostate lineage transitions, it remains unclear how upstream metabolic signalling contributes to the regulation of prostate epithelial identity. To fill this gap, we developed an approach to perform metabolomics on primary prostate epithelial cells. Using this approach, we discovered that the basal and luminal cells of the prostate exhibit distinct metabolomes and nutrient utilization patterns. Furthermore, basal-to-luminal differentiation is accompanied by increased pyruvate oxidation. We establish the mitochondrial pyruvate carrier and subsequent lactate accumulation as regulators of prostate luminal identity. Inhibition of the mitochondrial pyruvate carrier or supplementation with exogenous lactate results in large-scale chromatin remodelling, influencing both lineage-specific transcription factors and response to antiandrogen treatment. These results establish reciprocal regulation of metabolism and prostate epithelial lineage identity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Transportadores de Ácidos Monocarboxílicos Limite: Humans / Male Idioma: En Revista: Nat Cell Biol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Próstata / Transportadores de Ácidos Monocarboxílicos Limite: Humans / Male Idioma: En Revista: Nat Cell Biol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos