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

ABSTRACT: 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. Notably, LD accumulation is prevented, and tumor burden reduced in vivo upon concurrent inhibition of MYC signaling and glutamine metabolism. 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 discoveries provide an attractive approach for development of new therapeutic interventions for the treatment of this type of renal cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223069 | GEO | 2024/01/27

REPOSITORIES: GEO

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2022-03-01 | PXD001552 | Pride

Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels

2012-06-09 | GSE38590 | GEO

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Investigating NAFLD from RNA-seq data (human cell line Huh7) for samples under three treatments: low fat low sugar, low fat high sugar and high fat high sugar. Wild type samples are compared against DGAT2 knocked out.

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2020-08-21 | E-MTAB-7884 | biostudies-arrayexpress

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