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

Significance Lipid droplet (LD) accumulation is common in clear cell renal cell carcinoma (ccRCC), providing survival advantage and association with aggressiveness. However, the mechanisms controlling their biogenesis remain poorly known. Understanding their formation is crucial for developing targeted strategies. We show that MYC inhibition in ccRCC resulted in increased triglyceride accumulation in LDs in a glutamine-dependent process driven by enhanced HILPDA expression. Downregulation of HILPDA reduced tumor growth, and it was only highly expressed in ccRCC in comparison with other tumors or healthy renal tissue. Collectively, we highlight the role of MYC expression and glutamine metabolism in LD biogenesis and propose HILPDA as a specific target for precision medicine, providing an attractive therapeutic approach for this aggressive malignancy.

• Publication year

  2024

• Venue

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

• Publication date

  2024-02-09

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1073/pnas.2310479121PMID 38335255PMCID 10873620
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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