Obesogenic high-fat diet and MYC cooperate to promote lactate accumulation and tumor microenvironment remodeling in prostate cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA838652 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19238277_1.fastq.gz | Fastqsanger.gz | |||
| SRR19238277_2.fastq.gz | Fastqsanger.gz | |||
| SRR19238278_1.fastq.gz | Fastqsanger.gz | |||
| SRR19238278_2.fastq.gz | Fastqsanger.gz | |||
| SRR19238279_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 40 |
Similar Datasets
Project description:<p>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 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 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 high-fat diet was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-L1+ tumor-associated macrophages and FOXP3+ regulatory T cells, as well as with the activation of transcriptional programs linked to disease progression and therapy resistance. Lactate itself also stimulated neoangiogenesis and prostate cancer cell migration, which were significantly reduced following treatment with the lactate dehydrogenase inhibitor FX11. In prostate cancer patients, high saturated fat intake and increased body mass index were associated with tumor glycolytic features that promote the infiltration of M2-like tumor-associated macrophages. Finally, upregulation of lactate dehydrogenase, indicative of a lactagenic phenotype, was associated with a shorter time to biochemical recurrence in independent clinical cohorts. This work identifies cooperation between genetic drivers and systemic metabolism to hijack the tumor microenvironment and promote prostate cancer progression through oncometabolite accumulation. This sets the stage for the assessment of lactate as a prognostic biomarker and supports strategies of dietary intervention and direct lactagenesis blockade in treating advanced prostate cancer.</p><p><br></p><p><strong>Murine serum assays</strong> are reported in the current study <strong>MTBLS3316</strong>.</p><p><strong>Murine prostate assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS3317' rel='noopener noreferrer' target='_blank'><strong>MTBLS3317</strong></a>.</p>
2024-04-10 | MTBLS3316 | MetaboLights
Project description:<p>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 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 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 high-fat diet was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-L1+ tumor-associated macrophages and FOXP3+ regulatory T cells, as well as with the activation of transcriptional programs linked to disease progression and therapy resistance. Lactate itself also stimulated neoangiogenesis and prostate cancer cell migration, which were significantly reduced following treatment with the lactate dehydrogenase inhibitor FX11. In prostate cancer patients, high saturated fat intake and increased body mass index were associated with tumor glycolytic features that promote the infiltration of M2-like tumor-associated macrophages. Finally, upregulation of lactate dehydrogenase, indicative of a lactagenic phenotype, was associated with a shorter time to biochemical recurrence in independent clinical cohorts. This work identifies cooperation between genetic drivers and systemic metabolism to hijack the tumor microenvironment and promote prostate cancer progression through oncometabolite accumulation. This sets the stage for the assessment of lactate as a prognostic biomarker and supports strategies of dietary intervention and direct lactagenesis blockade in treating advanced prostate cancer.</p><p><br></p><p><strong>Murine prostate assays</strong> are reported in the current study <strong>MTBLS3317</strong>.</p><p><strong>Murine serum assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS3316' rel='noopener noreferrer' target='_blank'><strong>MTBLS3316</strong></a>.</p>
2024-04-10 | MTBLS3317 | MetaboLights
Project description:In this study, we investigated the effect of high-fat diet on prostate cancer progression. We specifically analyzed the metabolome, transcriptome, and tumor microenvironment of MYC transgenic and wild-type mice subjected to high-fat diet (enriched in saturated fat) and control diet for 21 weeks.
2024-04-08 | GSE203139 | GEO
Project description:Wound healing is associated with high rates of cell replication and lactate accumulation even under normoxic and hyperoxic conditions. Lactate accounts for various effects in tissue regeneration, such as collagen synthesis, angiogenesis, modulation of cytokine patterns and as recently shown for stem cell homing. Its influence on genes involved in cell replication has not been shown yet. Therefore, the effect of lactate considering genes involved in different cellular processes was investigated. Human umbilical vein endothelial cells (HUVEC) were cultured and incubated with lactate for different periods of time. Gene expression analysis was performed using custom-designed oligonucleotide microarrays. Keywords: Human gene expression study Reference design with Cy3 labeled uniRNA and Cy5 labeled sample RNA.
2010-05-15 | E-GEOD-11458 | biostudies-arrayexpress
Project description:We treated mESCs with 50mM lactate to examine its impact on mESC epigenome. Interestingly, we found that lactate supplementation stimulated H3K18 lactylation accumulation on a subset of genes, which in turn promoted transcriptional elongation. Our results indicate that lactate supplementation expands transcriptional network of mouse ESCs.
2022-02-01 | GSE192358 | GEO
Project description:Wound healing is associated with high rates of cell replication and lactate accumulation even under normoxic and hyperoxic conditions. Lactate accounts for various effects in tissue regeneration, such as collagen synthesis, angiogenesis, modulation of cytokine patterns and as recently shown for stem cell homing. Its influence on genes involved in cell replication has not been shown yet. Therefore, the effect of lactate considering genes involved in different cellular processes was investigated. Human umbilical vein endothelial cells (HUVEC) were cultured and incubated with lactate for different periods of time. Gene expression analysis was performed using custom-designed oligonucleotide microarrays. Keywords: Human gene expression study
2010-05-16 | GSE11458 | GEO
Project description:L. plantarum is known to possess an L-lactate inducible lactate racemase activity (Goffin et al. 2005. J. Bacteriol. 187:6750). In the present study, microarrays were used in order to identify all genes that are up-regulated by L-lactate, but not by a racemic mixture of D- and L-lactate. A mutant of L. plantarum NCIMB8826 deficient for NAD-dependent L-lactate activity (TF101; Ferain et al. 1994. 176:596), and thus producing no L-lactate, was grown in MRS medium at 28°C until mid-exponential phase (OD600nm 0.75). The culture was then divided into 3 sub-cultures. Optically pure sodium L-lactate (200 mM) was added to the first sub-culture (TF101 + L-lac 200 mM). An equimolar mixture of sodium D- and L-lactate (100 mM each) was added to the second sub-culture (TF101 + L/D-lac 200 mM). The third sub-culture was not treated (TF101; reference sample). The three sub-cultures were further incubated at 28°C for 1h30 (a time known to be sufficient for induction of lactate racemase activity by L-lactate). Cells were harvested by centrifugation. Microarray data were used ot identify genes that are specifically induced by L-lactate (comparison of TF101 with TF101 + L-lac 200 mM), but not by DL-lactate (comparison of TF101 with T101 + L/D-lac 200 mM). There are no biological replicates.
2013-07-01 | E-GEOD-43518 | biostudies-arrayexpress
Project description:L. plantarum is known to possess an L-lactate inducible lactate racemase activity (Goffin et al. 2005. J. Bacteriol. 187:6750). In the present study, microarrays were used in order to identify all genes that are up-regulated by L-lactate, but not by a racemic mixture of D- and L-lactate.
2013-07-01 | GSE43518 | GEO
Project description:Lactate is abundant in rapidly dividing cells, due to the requirement for elevated glucose catabolism to support proliferation. However, it is not known whether accumulated lactate affects the proliferative state. Here, we deploy a systematic approach to determine lactate-dependent regulation of proteins across the human proteome. From this data, we elucidate a mechanism of cell cycle regulation whereby accumulated lactate activates the anaphase promoting complex (APC/C). Remodeling of APC/C in this way is caused by direct inhibition of the SUMO protease SENP1 by lactate. We discover that accumulated lactate binds and inhibits SENP1 by forming a complex with zinc in the SENP1 active site. SENP1 inhibition by lactate stabilizes SUMOylation of two residues on APC4, which are required to reorient APC/C to allow UBE2C binding and thus increase APC/C activity. This direct regulation of APC/C by lactate is required to stimulate timed degradation of cell cycle proteins, and efficient mitotic exit in proliferative mammalian cells. The above mechanism is initiated upon mitotic entry when lactate abundance reaches its apex. In this way, accumulation of lactate communicates the consequences of a nutrient replete growth phase to stimulate timed opening of APC/C, cell division, and proliferation. Conversely, we show that aberrant remodeling of APC/C by lactate occurs when lactate concentrations are chronically elevated, which is a hallmark of numerous cancers. Moreover, persistent lactate accumulation overcomes anti-mitotic pharmacology to drive mitotic slippage via the newfound mode of APC/C activation. Taken together, we define a biochemical mechanism through which lactate directly regulates protein function to control cell cycle and proliferation.
2023-02-07 | PXD036641 | Pride
Project description:Double transgenic mice with hepatocyte-specific expression of AEG-1 and c-Myc show aggressive HCC compared to single transgenics. Gene expression was analyzed to understand the molecular mechanism by which AEG-1 and c-Myc cooperate to promote hepatocarcinogenesis. Livers were collected from naïve adult mice (3 mice/group). Total RNA was extrancted and subjected to RNA-Seq.
2014-09-30 | E-GEOD-61875 | biostudies-arrayexpress