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Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer.
Kim, Kyukwang; Khazan, Negar; Rowswell-Turner, Rachael B; Singh, Rakesh K; Moore, Taylor; Strawderman, Myla S; Miller, John P; Snyder, Cameron W A; Awada, Ahmad; Moore, Richard G.
Afiliación
  • Kim K; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
  • Khazan N; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
  • Rowswell-Turner RB; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
  • Singh RK; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
  • Moore T; Department of Biology, University of Rochester, Rochester, NY 14627, USA.
  • Strawderman MS; Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • Miller JP; Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, USA.
  • Snyder CWA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
  • Awada A; Department of Gynecologic Oncology, Adventhealth, Orlando, FL 32804, USA.
  • Moore RG; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14620, USA.
Cancers (Basel) ; 16(5)2024 Feb 28.
Article en En | MEDLINE | ID: mdl-38473335
ABSTRACT
Forchlorfenuron (FCF) is a widely used plant cytokinin that enhances fruit quality and size in agriculture. It also serves as a crucial pharmacological tool for the inhibition of septins. However, the precise target of FCF has not yet been fully determined. This study reveals a novel target of FCF and elucidates its downstream signaling events. FCF significantly impairs mitochondrial respiration and mediates metabolic shift toward glycolysis, thus making cells more vulnerable to glycolysis inhibition. Interestingly, FCF's impact on mitochondrial function persists, even in cells lacking septins. Furthermore, the impaired mitochondrial function leads to the degradation of HIF-1α, facilitated by increased cellular oxygen. FCF also induces AMPK activation, suppresses Erk1/2 phosphorylation, and reduces the expression of HER2, ß-catenin, and PD-L1. Endometrial cancer is characterized by metabolic disorders such as diabetes and aberrant HER2/Ras-Erk1/2/ß-catenin signaling. Thus, FCF may hold promise as a potential therapeutic in endometrial cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza