PEPCK-M recoups tumor cell anabolic potential in a PKC- ζ-dependent manner
ConclusionsAll in all, our data suggest that PEPCK-M might participate in the mechanisms to regulate proteostasis in the anabolic and stalling phases of tumor growth. We provide molecular clues into the clinical relevance of PEPCK-M as a mechanism of evasion of cancer cells in conditions of nutrient stress. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - January 7, 2021 Category: Cancer & Oncology Source Type: research
In vivo assessment of glutamine anaplerosis into the TCA cycle in human pre-malignant and malignant clonal plasma cells
ConclusionMeasurement of the in vivo activity of glutamine anaplerosis into the TCA cycle provides novel insight into the metabolic changes associated with the transformation of pre-malignant plasma cells in MGUS to malignant plasma cells in MM.Trial registrationNCT03384108 andNCT03119883 (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 11, 2020 Category: Cancer & Oncology Source Type: research
Estrogen-related receptor alpha directly binds to p53 and cooperatively controls colon cancer growth through the regulation of mitochondrial biogenesis and function
ConclusionsTherefore, our data suggest that by using the status of the p53 protein as a selection criterion, the ERR α/p53 transcriptional axis can be exploited as a metabolic vulnerability. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 10, 2020 Category: Cancer & Oncology Source Type: research
Protein synthesis inhibitors stimulate MondoA transcriptional activity by driving an accumulation of glucose 6-phosphate
ConclusionsOur data suggest that protein synthesis inhibitors rewire metabolism, resulting in an increase in mtATP and G6P, the latter driving MondoA-dependent transcriptional activity. Further, MondoA is a critical component of the cellular transcriptional response to RocA. Our functional assays suggest that RocA or similar translation inhibitors may show efficacy against ER − breast tumors and that the levels of MondoA and TXNIP should be considered when exploring these potential treatment options. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 4, 2020 Category: Cancer & Oncology Source Type: research
Deficiency of malate-aspartate shuttle component SLC25A12 induces pulmonary metastasis
ConclusionThis study highlights that certain branches of metabolism impact tumor growth and tumor metastasis differently. In addition, it also argues that commonly known metastasis indicators, including EMT genes, cell migration, or colony formation, do not always reflect metastatic capacity in vivo. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - November 26, 2020 Category: Cancer & Oncology Source Type: research
The effect of statin treatment on intratumoral cholesterol levels and LDL receptor expression: a window-of-opportunity breast cancer trial
ConclusionsThis study shows an upregulation of LDLR and preserved intratumoral cholesterol levels in breast cancer patients treated with statins. Together with previous findings on the anti-proliferative effect of statins in breast cancer, the present data suggest a potential role for LDLR in the statin-induced regulation of breast cancer cell proliferation.Trial registrationThe study has been registered at ClinicalTrials.gov (i.e., ID number:NCT00816244, NIH), December 30, 2008. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - November 23, 2020 Category: Cancer & Oncology Source Type: research
Treatment of glioblastoma multiforme with “classic” 4:1 ketogenic diet total meal replacement
ConclusionTreatment of GBM patients with 4:1 KD using total meal replacement program with standardized recipes was well tolerated. The small sample size limits efficacy conclusions.Trial registrationNCT01865162 registered 30 May 2013, and NCT02302235 registered 26 November 2014,https://clinicaltrials.gov/ (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - November 9, 2020 Category: Cancer & Oncology Source Type: research
Metabolic plasticity of IDH1 -mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition
ConclusionsMajor metabolic adaptations involved pathways that can generate glutamate by using alternative substrates from glutamine, such as alanine or aspartate. Indeed, asparagine synthetase was upregulated both in vivo and in vitro revealing a new potential therapeutic target for a combinatory approach with CB839 against IDH1mut gliomas. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - October 21, 2020 Category: Cancer & Oncology Source Type: research
Disruption of redox homeostasis for combinatorial drug efficacy in K-Ras tumors as revealed by metabolic connectivity profiling
ConclusionsOur findings open the way to develop metabolic connectivity profiling as a tool for a selective strategy of combined drug repositioning in precision oncology. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - September 28, 2020 Category: Cancer & Oncology Source Type: research
Body mass index-associated molecular characteristics involved in tumor immune and metabolic pathways
ConclusionOverall, our data indicated that BMI-associated molecular characteristics involved in tumor immune and metabolic pathways, which may highlight the clinical importance of considering BMI-associated molecular signatures in cancer precision medicine. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - September 24, 2020 Category: Cancer & Oncology Source Type: research
Metabolic plasticity imparts erlotinib-resistance in pancreatic cancer by upregulating glucose-6-phosphate dehydrogenase
In this study, we investigated the metabolic alterations in pancreatic cancer cells that do not respond to the EGFR inhibitor erlotinib. We selected erlotinib-resistant pancreatic cancer cells from MiaPaCa2 and AsPC1 cell lines. Metabolic profiling of erlotinib-resistant cells revealed a significant downregulation of glycolytic activity and reduced level of glycolytic metabolites compared to the sensitive cells. The resistant cells displayed elevated expression of the pentose phosphate pathway (PPP) enzymes involved in ROS regulation and nucleotide biosynthesis. The enhanced PPP elevated cellular NADPH/NADP+ ratio and prot...
Source: Cancer and Metabolism - September 20, 2020 Category: Cancer & Oncology Source Type: research
The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis
ConclusionsWe conclude that formate activates mTORC1 and induces pyrimidine synthesis via the mTORC1-dependent phosphorylation of CAD. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - September 20, 2020 Category: Cancer & Oncology Source Type: research
Glutamine uptake and utilization of human mesenchymal glioblastoma in orthotopic mouse model
ConclusionThus, our results outline the specific enhanced glutamine flux in vivo of the aggressive mesenchymal GBM subtype. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - August 9, 2020 Category: Cancer & Oncology Source Type: research
Correction to: Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells
An amendment to this paper has been published and can be accessed via the original article. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - August 9, 2020 Category: Cancer & Oncology Source Type: research
Fumarate hydratase-deficient renal cell carcinoma cells respond to asparagine by activation of the unfolded protein response and stimulation of the hexosamine biosynthetic pathway
ConclusionsAsn in the presence of Gln induces an ER stress response in FH-deficient UOK262 cells and stimulates increased synthesis of UDP-acetyl glycans indicative of HBP activity. These data demonstrate a novel effect of asparagine on cellular metabolism in FH-deficient cells that could be exploited therapeutically. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - August 2, 2020 Category: Cancer & Oncology Source Type: research
