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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma

Author

  • Lourdes Sainero-Alcolado
  • Elisa Garde-Lapido
  • Marteinn Thor Snaebjörnsson
  • Sarah Schoch
  • Irene Stevens
  • María Victoria Ruiz-Pérez
  • Christine Dyrager
  • Vicent Pelechano
  • Håkan Axelson
  • Almut Schulze
  • Marie Arsenian-Henriksson
Show all

Summary, in English

Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.

Department/s

  • LUCC: Lund University Cancer Centre
  • Division of Translational Cancer Research
  • Kidney cancer research group
  • Department of Laboratory Medicine

Publishing year

2024-02-13

Language

English

Pages

2310479121-2310479121

Publication/Series

Proceedings of the National Academy of Sciences of the United States of America

Volume

121

Issue

7

Document type

Journal article

Publisher

National Academy of Sciences

Topic

  • Medical Biotechnology

Keywords

  • clear cell renal cell carcinoma
  • glutamine
  • HILPDA
  • lipid droplets
  • MYC

Status

Published

Research group

  • Kidney cancer research group

ISBN/ISSN/Other

  • ISSN: 1091-6490