Cancers have altered metabolism, and its investigation may uncover unique vulnerabilities. The <i>MYC</i> proto-oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). The role of MYC in metabolic changes involved in initiation, maintenance, and progression of RCC remains vague. By employing desorption electrospray ionization mass spectrometric imaging (DESI-MSI) on our MYC-inducible RCC transgenic mouse model, we identify changes in lipid metabolism during the time-course of RCC initiation and progression. We find characteristic increases in the levels of glycerophosphoglycerols (PGs) and gradual elongation of fatty acid side chains of these glycerophospholipids with RCC progression. Concomitantly, we observe a suppression of several glycerophosphoinositol species (PIs). We also show that MYC orchestrates these changes through gene expression. Inhibition of MYC-induced lipogenesis depletes all DESI-detectable PGs and PIs. It prevents RCC tumorigenesis and causes RCC regression in both our transgenic mouse model and human RCC xenografts. We conclude that MYC causes dependence upon phospholipid metabolism that can be therapeutically targeted to remediate kidney cancer.

Inhibition of MYC-induced lipogenesis prevents renal cell carcinoma initiation and progression

253rd National Meeting (2017)

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