132 results match your criteria Cancer Metab[Journal]


Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer.

Cancer Metab 2020 19;8:11. Epub 2020 Jun 19.

Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Princess Alexandra Hospital, Translational Research Institute, Brisbane, Australia.

Background: Metabolic reprograming, non-mutational epigenetic changes, increased cell plasticity, and multidrug tolerance are early hallmarks of therapy resistance in cancer. In this temporary, therapy-tolerant state, cancer cells are highly sensitive to ferroptosis, a form of regulated cell death that is caused by oxidative stress through excess levels of iron-dependent peroxidation of polyunsaturated fatty acids (PUFA). However, mechanisms underpinning therapy-induced ferroptosis hypersensitivity remain to be elucidated. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-020-00217-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304214PMC

PHGDH supports liver ceramide synthesis and sustains lipid homeostasis.

Cancer Metab 2020 15;8. Epub 2020 Jun 15.

Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA.

Background: d-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown.

Methods: To study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-020-00212-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294658PMC

Common biochemical properties of metabolic genes recurrently dysregulated in tumors.

Cancer Metab 2020 8;8. Epub 2020 May 8.

1Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48105 USA.

Background: Tumor initiation and progression are associated with numerous metabolic alterations. However, the biochemical drivers and constraints that contribute to metabolic gene dysregulation are unclear.

Methods: Here, we present MetOncoFit, a computational model that integrates 142 metabolic features that can impact tumor fitness, including enzyme catalytic activity, pathway association, network topology, and reaction flux. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-020-0211-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206696PMC

Metabolic regulation of calcium pumps in pancreatic cancer: role of phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3).

Cancer Metab 2020 2;8. Epub 2020 Apr 2.

1Division of Cancer Sciences, School of Medical Sciences, University Of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT UK.

Background: High glycolytic rate is a hallmark of cancer (Warburg effect). Glycolytic ATP is required for fuelling plasma membrane calcium ATPases (PMCAs), responsible for extrusion of cytosolic calcium, in pancreatic ductal adenocarcinoma (PDAC). Phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3) is a glycolytic driver that activates key rate-limiting enzyme Phosphofructokinase-1; we investigated whether PFKFB3 is required for PMCA function in PDAC cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-020-0210-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114799PMC

Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma.

Cancer Metab 2020 5;8. Epub 2020 Mar 5.

1Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA.

Background: Osteosarcoma (OS) is a malignant bone tumor that often develops during the period of rapid growth associated with adolescence. Despite successful primary tumor control accompanied by adjuvant chemotherapy, death from pulmonary metastases occurs in approximately 30% of patients within 5 years. As overall survival in patients remains unchanged over the last 30 years, urgent needs for novel therapeutic strategies exist. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-020-0209-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057558PMC

Metabolic models predict bacterial passengers in colorectal cancer.

Cancer Metab 2020 10;8. Epub 2020 Feb 10.

1Centre for Molecular and Biomolecular Informatics, Radboud University Medical Centre, Postbus 9101, 6500 HB Nijmegen, The Netherlands.

Background: Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial taxa are enriched in the metagenomes of CRC patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-020-0208-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008539PMC
February 2020

Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy.

Cancer Metab 2020 2;8. Epub 2020 Jan 2.

1Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109 USA.

Background: Metabolic programs in cancer cells are influenced by genotype and the tissue of origin. We have previously shown that central carbon metabolism is rewired in pancreatic ductal adenocarcinoma (PDA) to support proliferation through a glutamate oxaloacetate transaminase 1 (GOT1)-dependent pathway.

Methods: We utilized a doxycycline-inducible shRNA-mediated strategy to knockdown GOT1 in PDA and colorectal cancer (CRC) cell lines and tumor models of similar genotype. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0202-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941320PMC
January 2020

Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells.

Cancer Metab 2019 30;7:13. Epub 2019 Dec 30.

1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI USA.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options. Pyruvate kinase, especially the M2 isoform (PKM2), is highly expressed in PDAC cells, but its role in pancreatic cancer remains controversial. To investigate the role of pyruvate kinase in pancreatic cancer, we knocked down PKM2 individually as well as both PKM1 and PKM2 concurrently (PKM1/2) in cell lines derived from a pancreatic mouse model. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0205-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937848PMC
December 2019

A systematic flux analysis approach to identify metabolic vulnerabilities in human breast cancer cell lines.

Cancer Metab 2019 27;7:12. Epub 2019 Dec 27.

Metabolic Reprogramming Laboratory, Metabolic Research Unit, School of Medicine and Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria Australia.

Background: Increased flux through both glycolytic and oxidative metabolic pathways is a hallmark of breast cancer cells and is critical for their growth and survival. As such, targeting this metabolic reprograming has received much attention as a potential treatment approach. However, the heterogeneity of breast cancer cell metabolism, even within classifications, suggests a necessity for an individualised approach to treatment in breast cancer patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0207-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935091PMC
December 2019

HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells.

Cancer Metab 2019 27;7:11. Epub 2019 Dec 27.

Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9700RB The Netherlands.

Background: Hypoxia-inducible factors (HIF)1 and 2 are transcription factors that regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in hematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state.

Methods: Genome-wide ChIPseq and ChIP-PCR experiments were performed to identify HIF1 and HIF2 binding sites in human acute myeloid leukemia (AML) cells and healthy CD34 hematopoietic stem/progenitor cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0206-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935105PMC
December 2019

SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.

Cancer Metab 2019 11;7:10. Epub 2019 Dec 11.

1Department of Internal Medicine, School of Medicine, Yale University, PO Box 208020, TAC S269, New Haven, CT 06520 USA.

Background: Obesity confers an increased risk and accelerates the progression of multiple tumor types in rodents and humans, including both breast and colon cancer. Because sustained weight loss is rarely achieved, therapeutic approaches to slow or prevent obesity-associated cancer development have been limited, and mechanistic insights as to the obesity-cancer connection have been lacking.

Methods: E0771 breast tumors and MC38 colon tumors were treated in vivo in mice and in vitro with two mechanistically different insulin-lowering agents, a controlled-release mitochondrial protonophore (CRMP) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, and tumor growth and glucose metabolism were assessed. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0203-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907191PMC
December 2019

A yeast phenomic model for the influence of Warburg metabolism on genetic buffering of doxorubicin.

Cancer Metab 2019 23;7. Epub 2019 Oct 23.

Department of Genetics, University of Alabama at Birmingham, Birmingham, AL USA.

Background: The influence of the Warburg phenomenon on chemotherapy response is unknown. mimics the Warburg effect, repressing respiration in the presence of adequate glucose. Yeast phenomic experiments were conducted to assess potential influences of Warburg metabolism on gene-drug interaction underlying the cellular response to doxorubicin. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0201-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806529PMC
October 2019

Inhibition of phosphoenolpyruvate carboxykinase blocks lactate utilization and impairs tumor growth in colorectal cancer.

Cancer Metab 2019 1;7. Epub 2019 Aug 1.

1Department of Pharmacological Sciences, Stony Brook University, 100 Nicolls Rd, Stony Brook, NY 11794 USA.

Background: Metabolic reprogramming is a key feature of malignant cells. While glucose is one of the primary substrates for malignant cells, cancer cells also display a remarkable metabolic flexibility. Depending on nutrient availability and requirements, cancer cells will utilize alternative fuel sources to maintain the TCA cycle for bioenergetic and biosynthetic requirements. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0199-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670241PMC
August 2019
2 Reads

CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism.

Cancer Metab 2019 16;7. Epub 2019 Jul 16.

1Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AH UK.

Background: Mitochondrial oxidative phosphorylation (OXPHOS) via the respiratory chain is required for the maintenance of tumour cell proliferation and regulation of epithelial to mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study, we interrogate the importance of CHCHD4-regulated mitochondrial metabolism for tumour cell proliferation and EMT-related phenotypes, and elucidate key pathways involved. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0200-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632184PMC
July 2019
1 Read

Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of .

Cancer Metab 2019 1;7. Epub 2019 Jun 1.

1Department of Biomedicine, University of Bergen, Bergen, Norway.

Background: Epithelial to mesenchymal transition (EMT) is a well-characterized process of cell plasticity that may involve metabolic rewiring. In cancer, EMT is associated with malignant progression, tumor heterogeneity, and therapy resistance. In this study, we investigated the role of succinate dehydrogenase (SDH) as a potential key regulator of EMT. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0197-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544948PMC
June 2019
9 Reads

-mutated cancers are sensitive to the green tea polyphenol epigallocatechin-3-gallate.

Cancer Metab 2019 20;7. Epub 2019 May 20.

2Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 26, 6525 Nijmegen, GA The Netherlands.

Background: Mutations in isocitrate dehydrogenase 1 () occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of -2-hydroxyglutarate (2-HG) at the expense of α-ketoglutarate (α-KG) and NADPH. To overcome metabolic stress induced by these alterations, -mutated ( ) cancers utilize rescue mechanisms comprising pathways in which glutaminase and glutamate dehydrogenase (GLUD) are involved. We hypothesized that inhibition of glutamate processing with the pleiotropic GLUD-inhibitor epigallocatechin-3-gallate (EGCG) would not only hamper 2-HG production, but also decrease NAD(P)H and α-KG synthesis in cancers, resulting in increased metabolic stress and increased sensitivity to radiotherapy. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-019-0198-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526618PMC
May 2019
13 Reads

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.

Cancer Metab 2019 9;7. Epub 2019 May 9.

Laboratorio de Estudios de Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.

Background: Breast cancer (BC) is the most common female cancer and the leading cause of cancer death in women worldwide. Alterations in epithelial cadherin (E-cadherin) expression and functions are associated to BC, but the underlying molecular mechanisms have not been fully elucidated. We have previously reported a novel human E-cadherin splice variant (E-cadherin variant) mRNA. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0196-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507066PMC
May 2019
2 Reads

Stratification of cancer and diabetes based on circulating levels of formate and glucose.

Cancer Metab 2019 24;7. Epub 2019 Apr 24.

1Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD UK.

Background: Serum and urine metabolites have been investigated for their use as cancer biomarkers. The specificity of candidate metabolites can be limited by the impact of other disorders on metabolite levels. In particular, the increasing incidence of obesity could become a significant confounding factor. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-019-0195-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482583PMC
April 2019
2 Reads

CHCHD4 confers metabolic vulnerabilities to tumour cells through its control of the mitochondrial respiratory chain.

Cancer Metab 2019 6;7. Epub 2019 Mar 6.

Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0AH UK.

Background: Tumour cells rely on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to survive. Thus, mitochondrial OXPHOS has become an increasingly attractive area for therapeutic exploitation in cancer. However, mitochondria are required for intracellular oxygenation and normal physiological processes, and it remains unclear which mitochondrial molecular mechanisms might provide therapeutic benefit. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-019-0194-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404347PMC
March 2019
17 Reads

The novel function of tumor protein D54 in regulating pyruvate dehydrogenase and metformin cytotoxicity in breast cancer.

Cancer Metab 2019 24;7. Epub 2019 Jan 24.

1Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 USA.

Background: The role of tumor protein D54 in breast cancer has not been studied and its function in breast cancer remains unclear. In our previous pharmacogenomic studies using lymphoblastoid cell line (LCL), this protein has been identified to affect metformin response. Although metformin has been widely studied as a prophylactic and chemotherapeutic drug, there is still a lack of biomarkers predicting the response to metformin in breast cancer. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0193-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345044PMC
January 2019
1 Read

Transport-exclusion pharmacology to localize lactate dehydrogenase activity within cells.

Cancer Metab 2018 12;6:19. Epub 2018 Dec 12.

1Department of Chemistry, Washington University, St. Louis, USA.

Background: Recent and work has shown that lactate provides an important source of carbon for metabolic reactions in cancer cell mitochondria. An interesting question is whether lactate is oxidized by lactate dehydrogenase (LDH) in the cytosol and/or in mitochondria. Since metabolic processes in the cytosol and mitochondria are affected by redox balance, the location of LDH may have important regulatory implications in cancer metabolism. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0192-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290536PMC
December 2018
21 Reads

p53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant.

Cancer Metab 2018 3;6:18. Epub 2018 Dec 3.

2Francis Crick Institute, 1 Midland Road, London, NW1 1AT UK.

Background: In response to oncogenic stress, the tumour suppressor protein p53 can induce the elimination of cells through induction of cell death or senescence, helping to restrain malignant progression. Conversely, under nutrient stress, p53 can protect cells by supporting metabolic adaptation. Many cancers express mutant p53 proteins that have lost the cell-elimination properties of wild-type p53. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0191-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276204PMC
December 2018
4 Reads

Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer.

Cancer Metab 2018 15;6:14. Epub 2018 Nov 15.

1Division of Medical Oncology, Duke University Medical Center, 3008 Snyderman Building, 905 S. LaSalle St, Durham, NC 27710 USA.

Background: While self-reported exercise is associated with a reduction in the risk of recurrence in colorectal cancer, the molecular mechanisms underpinning this relationship are unknown. Furthermore, the effect of exercise on intratumoral metabolic processes has not been investigated in detail in human cancers. In our current study, we generated six colorectal patient patient-derived xenografts (CRC PDXs) models and treated each PDX to voluntary wheel running (exercise) for 6-8 weeks or no exposure to the wheel (control). Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0190-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237036PMC
November 2018
45 Reads

Switch to low-fat diet improves outcome of acute lymphoblastic leukemia in obese mice.

Cancer Metab 2018 1;6:15. Epub 2018 Nov 1.

1Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA USA.

Background: It is becoming increasingly recognized that weight and nutritional status can impact cancer survival. We have previously shown that obese mice with syngeneic acute lymphoblastic leukemia (ALL) have poorer response to chemotherapy treatment than control mice. We therefore investigated whether dietary intervention could improve outcome from the most common pediatric cancer, ALL. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0189-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211598PMC
November 2018
22 Reads

PKM2 is not required for pancreatic ductal adenocarcinoma.

Cancer Metab 2018 23;6:17. Epub 2018 Oct 23.

1Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.

Background: While most cancer cells preferentially express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2), PKM2 is dispensable for tumor development in several mouse cancer models. PKM2 is expressed in human pancreatic cancer, and there have been conflicting reports on the association of PKM2 expression and pancreatic cancer patient survival, but whether PKM2 is required for pancreatic cancer progression is unknown. To investigate the role of PKM2 in pancreatic cancer, we used a conditional allele to delete PKM2 in a mouse model of pancreatic ductal adenocarcinoma (PDAC). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0188-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198443PMC
October 2018
2 Reads

Hepatocellular carcinoma-associated hypercholesterolemia: involvement of proprotein-convertase-subtilisin-kexin type-9 (PCSK9).

Cancer Metab 2018 25;6:16. Epub 2018 Oct 25.

1Laboratory No. 6, National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, 411 007 India.

Background: PCSK9 regulates low-density lipoprotein cholesterol (LDLc) level and has been implicated in hypercholesterolemia. Aberrant plasma lipid profile is often associated with various cancers. Clinically, the relationship between altered serum lipid level and hepatocellular carcinoma (HCC) has been documented; however, the underlying cause and implications of such dyslipidemia remain unclear. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0187-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201570PMC
October 2018
18 Reads

Protein interaction and functional data indicate MTHFD2 involvement in RNA processing and translation.

Cancer Metab 2018 27;6:12. Epub 2018 Sep 27.

1Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.

Background: The folate-coupled metabolic enzyme MTHFD2 is overexpressed in many tumor types and required for cancer cell proliferation, and is therefore of interest as a potential cancer therapeutic target. However, recent evidence suggests that MTHFD2 has a non-enzymatic function which may underlie the dependence of cancer cells on this protein. Understanding this non-enzymatic function is important for optimal targeting of MTHFD2 in cancer. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0185-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158883PMC
September 2018
1 Read

CD38 is methylated in prostate cancer and regulates extracellular NAD.

Cancer Metab 2018 21;6:13. Epub 2018 Sep 21.

1Department of Molecular, Cell & Developmental Biology, University of California Los Angeles, Los Angeles, CA USA.

Background: Cancer cell metabolism requires sustained pools of intracellular nicotinamide adenine dinucleotide (NAD) which is maintained by a balance of NAD hydrolase activity and NAD salvage activity. We recently reported that human prostate cancer can be initiated following oncogene expression in progenitor-like luminal cells marked by low expression of the NAD-consuming enzyme CD38. CD38 expression is reduced in prostate cancer compared to benign prostate, suggesting that tumor cells may reduce CD38 expression in order to enhance pools of NAD. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0186-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150989PMC
September 2018
16 Reads

Activation of pro-survival metabolic networks by 1,25(OH)D does not hamper the sensitivity of breast cancer cells to chemotherapeutics.

Cancer Metab 2018 30;6:11. Epub 2018 Aug 30.

1Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.

Background: We have previously identified 1,25-dihydroxyvitamin D [1,25(OH)D], the bioactive form of vitamin D, as a potent regulator of energy-utilization and nutrient-sensing pathways in prostate cancer cells. In the current study, we investigated the effects of 1,25(OH)D on breast cancer (BCa) cell metabolism using cell lines representing distinct molecular subtypes, luminal (MCF-7 and T-47D), and triple-negative BCa (MDA-MB-231, MDA-MB-468, and HCC-1143).

Methods: 1,25(OH)D's effect on BCa cell metabolism was evaluated by employing a combination of real-time measurements of glycolysis/oxygen consumption rates using a biosensor chip system, GC/MS-based metabolomics, gene expression analysis, and assessment of overall energy levels. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0183-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116450PMC
August 2018
50 Reads

Hexokinase 2 is dispensable for T cell-dependent immunity.

Cancer Metab 2018 17;6:10. Epub 2018 Aug 17.

1Department of Medicine, Northwestern University Feinberg School of Medicine, McGaw Pavilion, Rm. M-334, 240 East Huron Street, Chicago, IL 60611 USA.

Background: T cells and cancer cells utilize glycolysis for proliferation. The hexokinase (1-4) family of enzymes catalyze the first step of glycolysis. Hexokinase 2 (HK2) is one of the most highly upregulated metabolic enzymes in both cancer and activated T cells. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0184-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098591PMC
August 2018
48 Reads

Inflammation-induced DNA methylation of DNA polymerase gamma alters the metabolic profile of colon tumors.

Cancer Metab 2018 10;6. Epub 2018 Jul 10.

1Medical Sciences, Indiana University School of Medicine, Bloomington, Indiana USA.

Background: Inflammation, metabolism, and epigenetic modulation are highly interconnected processes that can be altered during tumorigenesis. However, because of the complexity of these interactions, direct cause and effect during tumorigenesis have been difficult to prove. Previously, using a murine model of inflammation-induced colon tumorigenesis, we determined that the promoter of the catalytic subunit of DNA polymerase gamma () is DNA hypermethylated and silenced in inflammation-induced tumors, but not in non-inflammation-induced (mock) tumors, suggesting that inflammation can induce silencing of through promoting DNA methylation during tumorigenesis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0182-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038244PMC
July 2018
68 Reads

A precision therapeutic strategy for hexokinase 1-null, hexokinase 2-positive cancers.

Cancer Metab 2018 28;6. Epub 2018 Jun 28.

1Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 USA.

Background: Precision medicine therapies require identification of unique molecular cancer characteristics. Hexokinase (HK) activity has been proposed as a therapeutic target; however, different hexokinase isoforms have not been well characterized as alternative targets. While HK2 is highly expressed in the majority of cancers, cancer subtypes with differential HK1 and HK2 expression have not been characterized for their sensitivities to HK2 silencing. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0181-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022704PMC
June 2018
6 Reads

Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation.

Cancer Metab 2018 11;6. Epub 2018 Jun 11.

1Department of Obstetrics and Gynaecology, University Hospital of Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany.

Background: Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0180-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996481PMC
June 2018
13 Reads

Isoform-specific deletion of PKM2 constrains tumor initiation in a mouse model of soft tissue sarcoma.

Cancer Metab 2018 31;6. Epub 2018 May 31.

1David H. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.

Background: Alternative splicing of the gene product generates the PKM1 and PKM2 isoforms of the glycolytic enzyme pyruvate kinase. PKM2 expression is associated with embryogenesis, tissue regeneration, and cancer. PKM2 is also the pyruvate kinase isoform expressed in most wild-type adult tissues, with PKM1 restricted primarily to skeletal muscle, heart, and brain. Read More

View Article

Download full-text PDF

Source
https://cancerandmetabolism.biomedcentral.com/articles/10.11
Publisher Site
http://dx.doi.org/10.1186/s40170-018-0179-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977456PMC
May 2018
14 Reads

Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities.

Cancer Metab 2018 17;6. Epub 2018 Apr 17.

2Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Room 379 Neuroscience Research Building, 635 Charles E. Young Dr. South, Los Angeles, CA 90095 USA.

Background: There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted to discern function by using cell lines transduced with exogenous IDH mutant enzyme, in this study, we perform unbiased metabolomics to discover metabolic differences between a cohort of patient-derived IDH1 mutant and IDH wildtype gliomaspheres.

Methods: Using both our own microarray and the TCGA datasets, we performed KEGG analysis to define pathways differentially enriched in IDH1 mutant and IDH wildtype cells and tumors. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0177-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905129PMC
April 2018
98 Reads

Metabolomics of oncogene-specific metabolic reprogramming during breast cancer.

Cancer Metab 2018 3;6. Epub 2018 Apr 3.

1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556 USA.

Background: The complex yet interrelated connections between cancer metabolism and oncogenic driver genes are relatively unexplored but have the potential to identify novel biomarkers and drug targets with prognostic and therapeutic value. The goal of this study was to identify global metabolic profiles of breast tumors isolated from multiple transgenic mouse models and to identify unique metabolic signatures driven by these oncogenes.

Methods: Using mass spectrometry (GC-MS, LC-MS/MS, and capillary zone electrophoresis (CZE)-MS platforms), we quantified and compared the levels of 374 metabolites in breast tissue from normal and transgenic mouse breast cancer models overexpressing a panel of oncogenes (PyMT, PyMT-DB, Wnt1, Neu, and C3-TAg). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0175-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881178PMC
April 2018
2 Reads

Mutant IDH1 gliomas downregulate phosphocholine and phosphoethanolamine synthesis in a 2-hydroxyglutarate-dependent manner.

Cancer Metab 2018 3;6. Epub 2018 Apr 3.

1Department of Radiology and Biomedical Imaging, University of California San Francisco, 1700 4th Street, Box 2532. Byers Hall 3rd Floor, Suite, San Francisco, CA 94143 USA.

Background: Magnetic resonance spectroscopy (MRS) studies have identified elevated levels of the phospholipid precursor phosphocholine (PC) and phosphoethanolamine (PE) as metabolic hallmarks of cancer. Unusually, however, PC and PE levels are reduced in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas that produce the oncometabolite 2-hydroxyglutarate (2-HG) relative to wild-type IDH1 (IDHwt) gliomas. The goal of this study was to determine the molecular mechanism underlying this unusual metabolic reprogramming in IDHmut gliomas. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0178-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881177PMC
April 2018
5 Reads

Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state.

Cancer Metab 2018 20;6. Epub 2018 Mar 20.

National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune, 411 007 India.

Background: Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, survival, proliferation, and invasiveness of cancer cells. However, the mechanistic link between these adipokines and therapeutic response in malignancies is not clearly understood. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0176-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859707PMC
March 2018
33 Reads

Cancer cell metabolic plasticity allows resistance to NAMPT inhibition but invariably induces dependence on LDHA.

Cancer Metab 2018 8;6. Epub 2018 Mar 8.

1Center For Integrative Biology (CIBIO), University of Trento, via Sommarive 9, Trento, Italy.

Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance.

Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-018-0174-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844108PMC
March 2018
32 Reads

Human mitochondrial MTHFD2 is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase.

Cancer Metab 2017 6;5:11. Epub 2017 Dec 6.

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712-0165 USA.

Background: Folate-dependent one-carbon metabolism provides one-carbon units for several biological processes. This pathway is highly compartmentalized in eukaryotes, with the mitochondrial pathway producing formate for use in cytoplasmic processes. The mitochondrial enzyme MTHFD2 has been reported to use NAD as a cofactor while the isozyme MTHFD2L utilizes NAD or NADP at physiologically relevant conditions. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0173-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718140PMC
December 2017
3 Reads

PKM2 is not required for colon cancer initiated by APC loss.

Cancer Metab 2017 30;5:10. Epub 2017 Nov 30.

Koch Institute for Integrative Cancer Research and the Department of Biology at Massachusetts Institute of Technology, Cambridge, MA 02139 USA.

Background: Cancer cells express the M2 isoform of the glycolytic enzyme pyruvate kinase (PKM2). PKM2 expression is not required for some cancers, and PKM2 loss can promote cancer progression; however, PKM2 has been reported to be essential in other tumor contexts, including a proposed non-metabolic role in β-catenin nuclear translocation. PKM2 is expressed in colon cancers where loss of the tumor suppressor results in β-catenin nuclear translocation and aberrant activation of the canonical Wnt signaling pathway. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0172-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707917PMC
November 2017
13 Reads

Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids.

Cancer Metab 2017 31;5. Epub 2017 Oct 31.

Scripps Center for Metabolomics, The Scripps Research Institute, La Jolla, CA USA.

Background: Cancer cells that enter the metastatic cascade require traits that allow them to survive within the circulation and colonize distant organ sites. As disseminating cancer cells adapt to their changing microenvironments, they also modify their metabolism and metabolite production.

Methods: A mouse xenograft model of spontaneous tumor metastasis was used to determine the metabolic rewiring that occurs between primary cancers and their metastases. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0171-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663111PMC
October 2017
13 Reads

Molecular features that predict the response to antimetabolite chemotherapies.

Cancer Metab 2017 3;5. Epub 2017 Oct 3.

Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710 USA.

Background: Antimetabolite chemotherapeutic agents that target cellular metabolism are widely used in the clinic and are thought to exert their anti-cancer effects mainly through non-specific cytotoxic effects. However, patients vary dramatically with respect to treatment outcome, and the sources of heterogeneity remain largely unknown.

Methods: Here, we introduce a computational method for identifying gene expression signatures of response to chemotherapies and apply it to human tumors and cancer cell lines. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0170-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627437PMC
October 2017
2 Reads

Bortezomib resistance in multiple myeloma is associated with increased serine synthesis.

Cancer Metab 2017 29;5. Epub 2017 Aug 29.

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.

Background: The proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy is restricted by the wide-spread occurrence of resistance. Metabolic alterations play an important role in cancer development and aid in the cellular adaptation to pharmacologically changed environments. Metabolic changes could therefore play an essential role in the development of drug resistance. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0169-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575874PMC
August 2017
30 Reads

Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities.

Cancer Metab 2017 22;5. Epub 2017 Aug 22.

Van Andel Research Institute, 333 Bostwick Ave, NE, Grand Rapids, MI 49503 USA.

Background: Among breast cancers, the triple-negative breast cancer (TNBC) subtype has the worst prognosis with no approved targeted therapies and only standard chemotherapy as the backbone of systemic therapy. Unique metabolic changes in cancer progression provide innovative therapeutic opportunities. The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), and MET receptor are highly expressed in TNBC, making both promising therapeutic targets. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0168-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568171PMC
August 2017
13 Reads

HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma.

Cancer Metab 2017 4;5. Epub 2017 Jul 4.

Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistökatu 6, 20520 Turku, Finland.

Background: A key feature of clear cell renal cell carcinoma (ccRCC) is the inactivation of the von Hippel-Lindau tumour suppressor protein (pVHL) that leads to the activation of hypoxia-inducible factor (HIF) pathway also in well-oxygenated conditions. Important regulator of HIF-α, prolyl hydroxylase PHD3, is expressed in high amounts in ccRCC. Although several functions and downstream targets for PHD3 in cancer have been suggested, the role of elevated PHD3 expression in ccRCC is not clear. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0167-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496173PMC
July 2017
17 Reads

The action of β-hydroxybutyrate on the growth, metabolism and global histone H3 acetylation of spontaneous mouse mammary tumours: evidence of a β-hydroxybutyrate paradox.

Cancer Metab 2017 28;5. Epub 2017 Feb 28.

Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE UK.

Background: Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth of some cancer cells and accelerates it in others. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0166-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331634PMC
February 2017
6 Reads

The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity.

Cancer Metab 2017 2;5. Epub 2017 Feb 2.

Dipartimento Farmacia e Biotecnologie (FABIT), Università di Bologna, Via Selmi 3, 40126 Bologna, Italy.

Deregulated 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 cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0165-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289018PMC
February 2017
22 Reads

Mitochondrial mutations and metabolic adaptation in pancreatic cancer.

Cancer Metab 2017 30;5. Epub 2017 Jan 30.

The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010 Australia.

Background: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-017-0164-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282905PMC
January 2017
57 Reads

Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.

Cancer Metab 2017 13;5. Epub 2017 Jan 13.

Discipline of Physiology, School of Medical Sciences & Bosch Institute, The Hub (D17), Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006 Australia.

Background: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood.

Results: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40170-016-0163-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237166PMC
January 2017
29 Reads