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MYC is a regulator of androgen receptor inhibition-induced metabolic requirements in prostate cancer.
Crowell, Preston D; Giafaglione, Jenna M; Jones, Anthony E; Nunley, Nicholas M; Hashimoto, Takao; Delcourt, Amelie M L; Petcherski, Anton; Agrawal, Raag; Bernard, Matthew J; Diaz, Johnny A; Heering, Kylie Y; Huang, Rong Rong; Low, Jin-Yih; Matulionis, Nedas; Navone, Nora M; Ye, Huihui; Zoubeidi, Amina; Christofk, Heather R; Rettig, Matthew B; Reiter, Robert E; Haffner, Michael C; Boutros, Paul C; Shirihai, Orian S; Divakaruni, Ajit S; Goldstein, Andrew S.
Afiliação
  • Crowell PD; Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Giafaglione JM; Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Jones AE; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Nunley NM; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hashimoto T; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Delcourt AML; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Petcherski A; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Agrawal R; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los
  • Bernard MJ; Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Diaz JA; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Heering KY; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Huang RR; Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Low JY; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Matulionis N; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Navone NM; Department of GU Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ye H; Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Zoubeidi A; Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada.
  • Christofk HR; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Stem Cell Research Center, University o
  • Rettig MB; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Reiter RE; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Haffner MC; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
  • Boutros PC; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los
  • Shirihai OS; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Clinical Biochemis
  • Divakaruni AS; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Goldstein AS; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, David Geffen School of Medicine, University of C
Cell Rep ; 42(10): 113221, 2023 10 31.
Article em En | MEDLINE | ID: mdl-37815914
ABSTRACT
Advanced prostate cancers are treated with therapies targeting the androgen receptor (AR) signaling pathway. While many tumors initially respond to AR inhibition, nearly all develop resistance. It is critical to understand how prostate tumor cells respond to AR inhibition in order to exploit therapy-induced phenotypes prior to the outgrowth of treatment-resistant disease. Here, we comprehensively characterize the effects of AR blockade on prostate cancer metabolism using transcriptomics, metabolomics, and bioenergetics approaches. The metabolic response to AR inhibition is defined by reduced glycolysis, robust elongation of mitochondria, and increased reliance on mitochondrial oxidative metabolism. We establish DRP1 activity and MYC signaling as mediators of AR-blockade-induced metabolic phenotypes. Rescuing DRP1 phosphorylation after AR inhibition restores mitochondrial fission, while rescuing MYC restores glycolytic activity and prevents sensitivity to complex I inhibition. Our study provides insight into the regulation of treatment-induced metabolic phenotypes and vulnerabilities in prostate cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias de Próstata Resistentes à Castração Limite: Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Neoplasias de Próstata Resistentes à Castração Limite: Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2023 Tipo de documento: Article