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Riscal R, Bull CJ, Mesaros C, et al. Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma. Cancer Discov. 2021;doi: 10.1158/2159-8290.CD-21-0211.
Riscal, R., Bull, C. J., Mesaros, C., Finan, J. M., Carens, M., Ho, E. S., Xu, J. P., Godfrey, J., Brennan, P., Johansson, M., Purdue, M. P., Chanock, S. J., Mariosa, D., Timpson, N. J., Vincent, E. E., Keith, B., Blair, I. A., Skuli, N., & Simon, M. C. (2021). Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma. Cancer discovery, . https://doi.org/10.1158/2159-8290.CD-21-0211
Riscal, Romain, et al. "Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma." Cancer discovery vol. (2021). doi: https://doi.org/10.1158/2159-8290.CD-21-0211
Riscal R, Bull CJ, Mesaros C, Finan JM, Carens M, Ho ES, Xu JP, Godfrey J, Brennan P, Johansson M, Purdue MP, Chanock SJ, Mariosa D, Timpson NJ, Vincent EE, Keith B, Blair IA, Skuli N, Simon MC. Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma. Cancer Discov. 2021 Jul 08; doi: 10.1158/2159-8290.CD-21-0211. Epub 2021 Jul 08. PMID: 34244212; PMCID: PMC8741905.
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Cancer Discov. 2021 Jul 08; doi: 10.1158/2159-8290.CD-21-0211. Epub 2021 Jul 08.

Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma.

Cancer discovery

Romain Riscal, Caroline J Bull, Clementina Mesaros, Jennifer M Finan, Madeleine Carens, Elaine S Ho, Jimmy P Xu, Jason Godfrey, Paul Brennan, Mattias Johansson, Mark P Purdue, Stephen J Chanock, Daniela Mariosa, Nicholas J Timpson, Emma E Vincent, Brian Keith, Ian A Blair, Nicolas Skuli, M Celeste Simon

Affiliations

  1. Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
  2. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.
  3. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  4. School of Translational Health Sciences, University of Bristol, Bristol, United Kingdom.
  5. Centers for Cancer Pharmacology and Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania.
  6. Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France.
  7. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
  8. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland.
  9. The Wistar Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
  10. Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania. [email protected].
  11. Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania.

PMID: 34244212 PMCID: PMC8741905 DOI: 10.1158/2159-8290.CD-21-0211

Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by large intracellular lipid droplets containing free and esterified cholesterol; however, the functional significance of cholesterol accumulation in ccRCC cells is unknown. We demonstrate that, surprisingly, genes encoding cholesterol biosynthetic enzymes are repressed in ccRCC, suggesting a dependency on exogenous cholesterol. Mendelian randomization analyses based on 31,000 individuals indicate a causal link between elevated circulating high-density lipoprotein (HDL) cholesterol and ccRCC risk. Depriving ccRCC cells of either cholesterol or HDL compromises proliferation and survival

©2021 American Association for Cancer Research.

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