Journal article

Multi-substrate Metabolic Tracing Reveals Marked Heterogeneity and Dependency on Fatty Acid Metabolism in Human Prostate Cancer

G Fidelito, DP De Souza, B Niranjan, W De Nardo, S Keerthikumar, K Brown, RA Taylor, MJ Watt

Molecular Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2023

Abstract

Cancer cells undergo metabolic reprogramming to meet tricarboxylic acid cycle through transaminase reactions before increased bioenergetic demands. Studies in cells and mice have being utilized via oxidative or reductive pathways. Blocking fatty highlighted the importance of oxidative metabolism and lipogenacid uptake or fatty acid oxidation with pharmacologic inhibitors esis in prostate cancer; however, the metabolic landscape of was sufficient to reduce cell viability in PDX-derived organoids, human prostate cancer remains unclear. To address this knowlwhereas blockade of DNL, or glucose or glutamine oxidation edge gap, we performed radiometric (14C) and stable (13C) isotope induced variab..

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Grants

Awarded by Victorian Cancer Agency


Funding Acknowledgements

This study was supported by the Cancer Council Victoria (Grant-in-aid, ID: APP1160217), the Prostate Cancer Foundation of Australia (ID: PCFA-NCG 3313, awarded to M.J. Watt, R.A. Taylor) the Diabetes Australia Research Trust (awarded to M.J. Watt). M.J. Watt was supported by the NHMRC of Australia (ID: APP1077703), and R.A. Taylor by the Victorian Cancer Agency (MCRF15023). MURAL was supported by the EJ. Whitten Foundation (RULE Prostate Cancer). G. Fidelito was supported by the Melbourne Research Scholarship (University of Melbourne).We gratefully acknowledge the members of the Melbourne Urological Research Alliance (MURAL), including Gail Risbridger and Mitchell Lawrence, the patients, families and consumers who support our research. We thank the members of the Prostate Cancer Research program Hong Wang, Samantha O'Dea and Ashlee Clark for technical assistance. We thank Malcolm J. McConville for helpful discussions. We acknowledge the contribution of the Metabolomics Australia facility and Victorian Centre for Functional Genomics (VCFG).The publication costs of this article were defrayed in part by the payment of publication fees. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.