2. Academic Validation
  3. HDAC7 promotes renal cancer progression by reprogramming branched-chain amino acid metabolism

HDAC7 promotes renal cancer progression by reprogramming branched-chain amino acid metabolism

  • Sci Adv. 2025 Jun 6;11(23):eadt3552. doi: 10.1126/sciadv.adt3552.
Hyeyoung Nam 1,  Anirban Kundu 2,  Suman Karki 1,  Richard L Kirkman 1,  Darshan S Chandrashekar 3,  Jeremy B Foote 4,  Guofang Zhang 5 6,  Wentao He 5,  Sooryanarayana Varambally 3,  Han-Fei Ding 3,  Sunil Sudarshan 1 7
Affiliations

Affiliations

  • 1 Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 2 Department of Urology and the University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
  • 3 Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 4 Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • 5 Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
  • 6 Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University Medical Center, Durham, NC, USA.
  • 7 Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.
PMID: 40465706 DOI: 10.1126/sciadv.adt3552
Abstract

Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney Cancer, exhibits notable metabolic reprogramming. We previously reported elevated HDAC7, a class II histone deacetylase, in ccRCC. Here, we demonstrate that HDAC7 promotes aggressive phenotypes and in vivo tumor progression in RCC. HDAC7 suppresses the expression of genes mediating branched-chain amino acid (BCAA) catabolism. Notably, lower expression of BCAA catabolism genes is strongly associated with worsened survival in ccRCC. Suppression of BCAA catabolism promotes expression of SNAIL1, a central mediator of aggressive phenotypes including migration and invasion. HDAC7-mediated suppression of the BCAA catabolic program promotes SNAI1 messenger RNA transcription via Notch signaling activation. Collectively, our findings provide innovative insights into the role of metabolic remodeling in ccRCC tumor progression.

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