Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells
ConclusionPKM1/2 knockdown does not impact the proliferation of pancreatic cancer cells. The serine biosynthesis pathway supports conversion of glucose to pyruvate during pyruvate kinase knockdown. However, direct conversion of serine to pyruvate was not observed during PKM1/2 knockdown. Investigating several alternative sources of pyruvate identified cysteine catabolism for pyruvate production during PKM1/2 knockdown. Surprisingly, we find that a large percentage of intracellular pyruvate comes from cysteine. Our results highlight the ability of PDAC cells to adaptively rewire their metabolic pathways during knockdown of ...
Source: Cancer and Metabolism - December 29, 2019 Category: Cancer & Oncology Source Type: research
A systematic flux analysis approach to identify metabolic vulnerabilities in human breast cancer cell lines
ConclusionsTogether, these data highlight that systematic flux analysis in breast cancer cells can identify targetable metabolic vulnerabilities, despite heterogeneity in metabolic profiles between individual cancer cell lines. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 26, 2019 Category: Cancer & Oncology Source Type: research
HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells
ConclusionThese data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state. In contrast, inhibition of BCR-ABL did impact on glucose consumption and lactate production regardless of the presence of HIFs. These data indicate that oncogene-mediated control over glycolysis can occur independently of hypoxic signaling modules. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 26, 2019 Category: Cancer & Oncology Source Type: research
SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia
ConclusionsTaken together, these data demonstrate that hyperinsulinemia per se promotes both breast and colon cancer progression in obese mice, and highlight SGLT2 inhibitors as a clinically available means of slowing obesity-associated tumor growth due to their glucose- and insulin-lowering effects. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 10, 2019 Category: Cancer & Oncology Source Type: research
A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin
ConclusionsWarburg status alters the genetic network required for yeast to buffer doxorubicin toxicity. Integration of yeast phenomic and cancer pharmacogenomics data suggests evolutionary conservation of gene-drug interaction networks and provides a new experimental approach to model their influence on chemotherapy response. Thus, yeast phenomic models could aid the development of precision oncology algorithms to predict efficacious cytotoxic drugs for cancer, based on genetic and metabolic profiles of individual tumors. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - October 22, 2019 Category: Cancer & Oncology Source Type: research
Inhibition of phosphoenolpyruvate carboxykinase blocks lactate utilization and impairs tumor growth in colorectal cancer
ConclusionsThese studies highlight lactate as an important substrate for CRC and the use of PEPCKi as a therapeutic approach to target lactate utilization in CRC cells. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 31, 2019 Category: Cancer & Oncology Source Type: research
CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism
ConclusionsCHCHD4 drives tumour cell growth and activates mTORC1 signalling through its control of respiratory chain mediated metabolism and complex I biology, and also regulates EMT-related phenotypes of tumour cells. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 15, 2019 Category: Cancer & Oncology Source Type: research
Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC
ConclusionsOur findings suggest that downregulation of SDHC promotes EMT and that this is accompanied by structural remodeling of the mitochondrial organelles. This may confer survival benefits upon exposure to hostile microenvironment including oxidative stress and hypoxia during cancer progression. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 31, 2019 Category: Cancer & Oncology Source Type: research
Isocitrate dehydrogenase 1 -mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate
ConclusionsThis work shows that glutamate can be directly processed intoD-2-HG and that reduction of glutamatolysis may be an effective and promising new treatment option forIDHmut cancers. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 19, 2019 Category: Cancer & Oncology Source Type: research
Characterization of the molecular changes associated with the overexpression of a novel epithelial cadherin splice variant mRNA in a breast cancer model using proteomics and bioinformatics approaches: identification of changes in cell metabolism and an increased expression of lactate dehydrogenase B
ConclusionsResults from this investigation contributed to further characterize molecular changes associated to the novel E-cadherin splice variant expression in BC cells. They also revealed an association between expression of the novel variant and changes related to BC progression and aggressiveness, in particular those associated to cell metabolism. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 8, 2019 Category: Cancer & Oncology Source Type: research
Stratification of cancer and diabetes based on circulating levels of formate and glucose
ConclusionsCirculating formate is reduced in HER2+ breast cancer, non-small cell lung cancer and highly obese patients relative to healthy controls. Further studies are required to determine the relevance of these observations in other cancer types and diseases. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - April 23, 2019 Category: Cancer & Oncology Source Type: research
CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain
ConclusionsOur study highlights an important role for CHCHD4 in regulating tumour cell metabolism and reveals that CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain and CI biology. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - March 5, 2019 Category: Cancer & Oncology Source Type: research
The novel function of tumor protein D54 in regulating pyruvate dehydrogenase and metformin cytotoxicity in breast cancer
ConclusionWe have discovered a novel mechanism by which TPD54 regulates pyruvate dehydrogenase and affects the sensitivity of breast cancer to metformin treatment. Our findings highlight the important post-translational regulation of PDK1 on PDH E1 α and the potential application of TPD54 as a biomarker for selecting tumors that may be sensitive to metformin therapy. These provide new insights into understanding the regulation of PDH complexes and the resistance mechanisms of cancer cells to metformin treatment. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - January 24, 2019 Category: Cancer & Oncology Source Type: research
Transport-exclusion pharmacology to localize lactate dehydrogenase activity within cells
ConclusionsOur results are consistent with some mitochondrial LDH that is accessible to oxamate, but inaccessible to GSK-2837808A until mitochondria are homogenized. This strategy of using inhibitors with selective access to subcellular compartments, which we refer to as transport-exclusion pharmacology, is broadly applicable to localize other metabolic reactions within cells. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 12, 2018 Category: Cancer & Oncology Source Type: research
p53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant
ConclusionOur work shows that mutant p53s can selectively retain wild-type p53 functions that allow adaptation to serine starvation through the activation of antioxidant defence pathways. Tumours containing this p53 mutation are resistant to serine-limited conditions and less responsive to therapy. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 3, 2018 Category: Cancer & Oncology Source Type: research
