biostudies-literatureBoufaied NDana-Farber Cancer InstituteCanadian Institutes of Health Research (CIHR)AIRC Foundation for Cancer ResearchWorld Cancer Research Fund InternationalU.S. Department of Defense (DOD)U.S. Department of DefenseDana-Farber Cancer Institute (DFCI)World Cancer Research Fund International (WCRF)Canadian Institutes of Health Research1834-1855https://www.ebi.ac.uk/biostudies/studies/S-EPMC11148549biostudies-literatureUnknown84(11)Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC-driven invasive prostate cancer through metabolic rewiring. Although c-MYC modulated key metabolic pathways, interaction with an obesogenic HFD was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-Cancer researchObesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer.PMC11148549PJT-180368PC150263IIG_FULL_2022_020IG-21966PJT-162246Claudia Adams Barr Award in Innovative Basic Cancer ResearchHallal TCacciatore SSabbioneda SBoufaied NZhao XLiu YHomsy KLabbe DPLuthold CMaga GLalli DImada ELSpratt DEMichelotti GBordeleau FNguyen QDDavicioni EButler LMGiunchi FEllis LStoraci AMde Polo APhotopoulos CDi Matteo AMucci LAGhigna CSyamala SHuang YLoda MChetta PSheridan PAMarchionni LVaira VZadra GfalseObesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer.Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC-driven invasive prostate cancer through metabolic rewiring. Although c-MYC modulated key metabolic pathways, interaction with an obesogenic HFD was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-2024-01-01T00:00:00Z2024 Jun2026-06-02T09:01:34.681Z2026-04-16T03:13:13.241ZS-EPMC111485493883175110.1158/0008-5472.CAN-23-0519