The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity
AbstractDeregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents a major modulator of electron transport chain activity and tricarboxylic acid cycle (TCA) flux, and is a pivotal enzyme in the metabolic reprogramming following a cancer cell’s change in bioenergetic requirements. By contributing to the control of α-ketoglutarate levels, dynamics, and oxidation state, the α-ketoglutarate dehydrogenase is also essential in modulating the epigenetic landscape of cancer cell...
Source: Cancer and Metabolism - February 1, 2017 Category: Cancer & Oncology Source Type: research
Mitochondrial mutations and metabolic adaptation in pancreatic cancer
ConclusionsThe heterogeneous genomic landscape of pancreatic tumours may converge on a common metabolic phenotype, with individual tumours adapting to increased anabolic demands via different genetic mechanisms. Targeting resulting metabolic phenotypes may be a productive therapeutic strategy. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - January 29, 2017 Category: Cancer & Oncology Source Type: research
Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
ConclusionsThese findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - January 12, 2017 Category: Cancer & Oncology Source Type: research
The role of tumor metabolism as a driver of prostate cancer progression and lethal disease: results from a nested case-control study
ConclusionsThe results suggest prostate cancer progression and lethal disease are associated with alterations in key metabolic signaling pathways. Pathways supporting proliferation appeared to be of particular importance in prostate tumor aggressiveness. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 6, 2016 Category: Cancer & Oncology Source Type: research
Weight control interventions improve therapeutic efficacy of dacarbazine in melanoma by reversing obesity-induced drug resistance
ConclusionsThis study indicates that obesity not only supports rapid melanoma progression but also impairs the outcome of chemotherapy, which can be improved upon employing weight control interventions. From clinically relevant point of view, our study exemplifies the importance of lifestyle interventions in the treatment of obesity-promoted cancers. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - December 6, 2016 Category: Cancer & Oncology Source Type: research
Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma
ConclusionsOur results characterize the metabolic reprogramming occurring during PDAC cell EMT and highlight the common changes of increased glucose uptake and lactate secretion under different EMT conditions. Such insight is urgently required for designing metabolic strategies to selectively target cells undergoing EMT in PDAC. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - October 16, 2016 Category: Cancer & Oncology Source Type: research
Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer
ConclusionsWe conclude that MCT-1 is part of a core Wnt signaling gene program for glycolysis in colon cancer and that modulation of this program could play an important role in shaping sensitivity to drugs that target cancer metabolism. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - October 2, 2016 Category: Cancer & Oncology Source Type: research
Starving cancer from the outside and inside: separate and combined effects of calorie restriction and autophagy inhibition on Ras-driven tumors
ConclusionsCombined restriction of extracellular (via CR in vivo or glucose deprivation in vitro) and intracellular (via autophagy inhibition) sources of energy and nutrients suppresses Ras-driven tumor growth more effectively than either CR or autophagy deficiency alone. Interventions targeting both systemic energy balance and tumor-cell intrinsic autophagy may represent a novel and effective anticancer strategy. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - September 15, 2016 Category: Cancer & Oncology Source Type: research
A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis
ConclusionsOur approach for the quantification of acetate is straightforward to implement using widely available equipment and reagents, and will aid in in-depth investigation of various aspects of acetate metabolism. It is also readily adaptable to the analysis of formate and short-chain fatty acids, making it highly relevant to the cancer metabolism community. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - September 1, 2016 Category: Cancer & Oncology Source Type: research
Metabolic requirements for cancer cell proliferation
ConclusionsOur analysis clarifies the differential needs for central carbon metabolism precursors, glutamine-derived nitrogen, and cofactors such as ATP, NADPH, and NAD+, while also providing justification for various extracellular nutrient uptake behaviors observed in tumors. Collectively, these results demonstrate how stoichiometric considerations alone can successfully predict empirically observed phenotypes and provide insight into biochemical dynamics that underlie responses to metabolic perturbations. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - August 17, 2016 Category: Cancer & Oncology Source Type: research
Malonate as a ROS product is associated with pyruvate carboxylase activity in acute myeloid leukaemia cells
ConclusionsThis study extends the interest in the PC activity in solid cancers to include leukaemias and further demonstrates the value of tracer-based NMR approaches in generating a more accurate picture of the flow of carbons and metabolites within the increasingly inappropriately named Krebs cycle. Moreover, our studies indicate that the PC activity in cancer cells can be exploited as an Achilles heel by using treatments, such as BaP, that elevate ROS production. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - August 3, 2016 Category: Cancer & Oncology Source Type: research
Novel drugs that target the metabolic reprogramming in renal cell cancer
Abstract
Molecular profiling studies of tumor tissue from patients with clear cell renal cell cancer (ccRCC) have revealed extensive metabolic reprogramming in this disease. Associations were found between metabolic reprogramming, histopathologic Fuhrman grade, and overall survival of patients. Large-scale genomics, proteomics, and metabolomic analyses have been performed to identify the molecular players in this process. Genes involved in glycolysis, the pentose phosphate pathway, glutamine metabolism, and lipogenesis were found to be upregulated in renal cell cancer (RCC) specimens as compared to norm...
Source: Cancer and Metabolism - July 12, 2016 Category: Cancer & Oncology Source Type: research
Fast exchange fluxes around the pyruvate node: a leaky cell model to explain the gain and loss of unlabelled and labelled metabolites in a tracer experiment
Conclusions
The current work established the possibility that a cell’s range of significant input substrates may be broader than anticipated. Metabolite exchange can affect intracellular enrichments. In particular, we showed that pyruvate was more strongly connected to lactate than to upstream glycolytic intermediates and that a fast lactate exchange may alter the outcome of flux analyses. Nevertheless, the leaky cell model may be an opportunity in disguise—the ability to continuously monitor metabolism using only the enrichments of extracellular metabolites. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 3, 2016 Category: Cancer & Oncology Source Type: research
Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes
Conclusions
Three naturally occurring metabolic clusters of breast cancer were detected among primary tumors from non-treated breast cancer patients. The clusters expressed differences in breast cancer-related protein as well as genes related to extracellular matrix and metabolic pathways known to be aberrant in cancer. Analyses of metabolic activity combined with gene and protein expression provide new information about the heterogeneity of breast tumors and, importantly, the metabolic differences infer that the clusters may be susceptible to different metabolically targeted drugs. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - June 26, 2016 Category: Cancer & Oncology Source Type: research
Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool
Conclusions
Stool metabolite profiles were limited for direct associations with CRC and adjacent mucosa, yet metabolic pathways were conserved across both matrices. Larger patient-matched CRC, adjacent non-cancerous colonic mucosa, and stool cohort studies for metabolite profiling are needed to validate these small molecule differences and metabolic pathway aberrations for clinical application to CRC control, treatment, and prevention. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - June 5, 2016 Category: Cancer & Oncology Source Type: research
