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  • Metabolic plasticity of IDH1-mutant glioma cell lines is responsible for low sensitivity to glutaminase inhibition
    Cancer Metab. (IF 5.033) Pub Date : 2020-10-21
    Victor Ruiz-Rodado; Adrian Lita; Tyrone Dowdy; Orieta Celiku; Alejandra Cavazos Saldana; Herui Wang; Chun Zhang Yang; Raj Chari; Aiguo Li; Wei Zhang; Hua Song; Meili Zhang; Susie Ahn; Dionne Davis; Xiang Chen; Zhengping Zhuang; Christel Herold-Mende; Kylie J. Walters; Mark R. Gilbert; Mioara Larion

    Targeting glutamine metabolism in cancer has become an increasingly vibrant area of research. Mutant IDH1 (IDH1mut) gliomas are considered good candidates for targeting this pathway because of the contribution of glutamine to their newly acquired function: synthesis of 2-hydroxyglutarate (2HG). We have employed a combination of 13C tracers including glutamine and glucose for investigating the metabolism

    更新日期:2020-10-27
  • Disruption of redox homeostasis for combinatorial drug efficacy in K-Ras tumors as revealed by metabolic connectivity profiling
    Cancer Metab. (IF 5.033) Pub Date : 2020-09-29
    Daniela Gaglio; Marcella Bonanomi; Silvia Valtorta; Rohit Bharat; Marilena Ripamonti; Federica Conte; Giulia Fiscon; Nicole Righi; Elisabetta Napodano; Federico Papa; Isabella Raccagni; Seth J. Parker; Ingrid Cifola; Tania Camboni; Paola Paci; Anna Maria Colangelo; Marco Vanoni; Christian M. Metallo; Rosa Maria Moresco; Lilia Alberghina

    Rewiring of metabolism induced by oncogenic K-Ras in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways. We performed mass spectrometric metabolomics analysis in vitro and in vivo

    更新日期:2020-09-29
  • Body mass index-associated molecular characteristics involved in tumor immune and metabolic pathways
    Cancer Metab. (IF 5.033) Pub Date : 2020-09-25
    Chao Hu; Xiong Chen; Chengyun Yao; Yu Liu; Haojun Xu; Guoren Zhou; Hongping Xia; Jinglin Xia

    Overweight or obesity has been evidenced as an important risk factor involved in the incidence, mortality, and therapy response of multiple malignancies. However, the differences between healthy and obesity tumor patients at the molecular and multi-omics levels remain unclear. Our study performed a comprehensive and multidimensional analysis in fourteen tumor types of The Cancer Genome Atlas (TCGA)

    更新日期:2020-09-25
  • The conversion of formate into purines stimulates mTORC1 leading to CAD-dependent activation of pyrimidine synthesis
    Cancer Metab. (IF 5.033) Pub Date : 2020-09-21
    Jacqueline Tait-Mulder; Kelly Hodge; David Sumpton; Sara Zanivan; Alexei Vazquez

    Mitochondrial serine catabolism to formate induces a metabolic switch to a hypermetabolic state with high rates of glycolysis, purine synthesis and pyrimidine synthesis. While formate is a purine precursor, it is not clear how formate induces pyrimidine synthesis. Here we combine phospho-proteome and metabolic profiling to determine how formate induces pyrimidine synthesis. We discover that formate

    更新日期:2020-09-21
  • Metabolic plasticity imparts erlotinib-resistance in pancreatic cancer by upregulating glucose-6-phosphate dehydrogenase
    Cancer Metab. (IF 5.033) Pub Date : 2020-09-21
    Neha Sharma; Alok Bhushan; Jun He; Gagan Kaushal; Vikas Bhardwaj

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant forms of cancer. Lack of effective treatment options and drug resistance contributes to the low survival among PDAC patients. 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

    更新日期:2020-09-21
  • Correction to: Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells.
    Cancer Metab. (IF 5.033) Pub Date : 2020-08-10
    Masahiro Kawashima,Karim Bensaad,Christos E Zois,Alessandro Barberis,Esther Bridges,Simon Wigfield,Christoffer Lagerholm,Ruslan I Dmitriev,Mariko Tokiwa,Masakazu Toi,Dmitri B Papkovsky,Francesca M Buffa,Adrian L Harris

    An amendment to this paper has been published and can be accessed via the original article.

    更新日期:2020-08-10
  • Glutamine uptake and utilization of human mesenchymal glioblastoma in orthotopic mouse model.
    Cancer Metab. (IF 5.033) Pub Date : 2020-08-10
    Kristell Oizel,Chendong Yang,Ophelie Renoult,Fabien Gautier,Quyen N Do,Noemie Joalland,Xiaofei Gao,Bookyung Ko,François Vallette,Woo-Ping Ge,François Paris,Ralph J DeBerardinis,Claire Pecqueur

    Glioblastoma (GBM) are highly heterogeneous on the cellular and molecular basis. It has been proposed that glutamine metabolism of primary cells established from human tumors discriminates aggressive mesenchymal GBM subtype to other subtypes. To study glutamine metabolism in vivo, we used a human orthotopic mouse model for GBM. Tumors evolving from the implanted primary GBM cells expressing different

    更新日期:2020-08-10
  • Fumarate hydratase-deficient renal cell carcinoma cells respond to asparagine by activation of the unfolded protein response and stimulation of the hexosamine biosynthetic pathway.
    Cancer Metab. (IF 5.033) Pub Date : 2020-08-03
    Rony Panarsky,Daniel R Crooks,Andrew N Lane,Youfeng Yang,Teresa A Cassel,Teresa W-M Fan,W Marston Linehan,Jeffrey A Moscow

    The loss-of-function mutation of fumarate hydratase (FH) is a driver of hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Fumarate accumulation results in activation of stress-related mechanisms leading to upregulation of cell survival-related genes. To better understand how cells compensate for the loss of FH in HLRCC, we determined the amino acid nutrient requirements of the FH-deficient

    更新日期:2020-08-03
  • Fine-tuning the metabolic rewiring and adaptation of translational machinery during an epithelial-mesenchymal transition in breast cancer cells.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-19
    Tamara Fernández-Calero,Marcos Davyt,Karen Perelmuter,Cora Chalar,Giovana Bampi,Helena Persson,Juan Pablo Tosar,Völundur Hafstað,Hugo Naya,Carlos Rovira,Mariela Bollati-Fogolín,Ricardo Ehrlich,Gilles Flouriot,Zoya Ignatova,Mónica Marín

    During breast cancer progression, the epithelial to mesenchymal transition has been associated with metastasis and endocrine therapy resistance; however, the underlying mechanisms remain elusive. To gain insight into this process, we studied the transition undergone by MCF7-derived cells, which is driven by the constitutive nuclear expression of a MKL1 variant devoid of the actin-binding domain (MKL1

    更新日期:2020-07-24
  • Treatment of ErbB2 breast cancer by mitochondrial targeting.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-14
    Sophia Eldad,Rachel Hertz,Gilad Vainer,Ann Saada,Jacob Bar-Tana

    ErbB2 breast cancer still remains an unmet need due to primary and/or acquired resistance to current treatment strategies. MEDICA compounds consist of synthetic long-chain α,ω-dicarboxylic acids previously reported to suppress breast cancer in PyMT transgenic mice. MEDICA efficacy and mode of action in the ErbB2 context was studied in ErbB2 transgenic mice and human breast cancer cells. MEDICA treatment

    更新日期:2020-07-24
  • Fructose contributes to the Warburg effect for cancer growth.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-10
    Takahiko Nakagawa,Miguel A Lanaspa,Inigo San Millan,Mehdi Fini,Christopher J Rivard,Laura G Sanchez-Lozada,Ana Andres-Hernando,Dean R Tolan,Richard J Johnson

    Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated

    更新日期:2020-07-24
  • Metabolite AutoPlotter - an application to process and visualise metabolite data in the web browser.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-10
    Matthias Pietzke,Alexei Vazquez

    Metabolomics is gaining popularity as a standard tool for the investigation of biological systems. Yet, parsing metabolomics data in the absence of in-house computational scientists can be overwhelming and time-consuming. As a consequence of manual data processing, the results are often not analysed in full depth, so potential novel findings might get lost. To tackle this problem, we developed Metabolite

    更新日期:2020-07-24
  • Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-06
    Masahiro Kawashima,Karim Bensaad,Christos E Zois,Alessandro Barberis,Esther Bridges,Simon Wigfield,Christoffer Lagerholm,Ruslan I Dmitriev,Mariko Tokiwa,Masakazu Toi,Dmitri B Papkovsky,Francesca M Buffa,Adrian L Harris

    Humans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Previously, we found that the knockdown of hypoxia-inducible

    更新日期:2020-07-24
  • Metformin sensitizes therapeutic agents and improves outcome in pre-clinical and clinical diffuse large B-cell lymphoma.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-06
    Anil R Singh,Juan J Gu,Qunling Zhang,Pallawi Torka,Suchitra Sundaram,Cory Mavis,Francisco J Hernandez-Ilizaliturri

    The treatment of diffuse large B-cell lymphoma (DLBCL) is limited by the development of resistance to therapy, and there is a need to develop novel therapeutic strategies for relapsed and refractory aggressive lymphoma. Metformin is an oral agent for type 2 diabetes that has been shown to decrease cancer risk and lower mortality in other types of cancer. We performed a retrospective analysis of the

    更新日期:2020-07-24
  • Tumor-associated collagen signatures: pushing tumor boundaries.
    Cancer Metab. (IF 5.033) Pub Date : 2020-07-02
    Elizabeth A Brett,Matthias A Sauter,Hans-Günther Machens,Dominik Duscher

    In 2006, a new model of invasive breast tumor emerged and, since 2011, is gaining recognition and research momentum. “Tumor-associated collagen signatures” describe 3 distinct layers of collagen which radiate outward in shells from the main body of the tumor. The outermost layer (TACS3) features branches of collagen radiating away from the tumor, 90° perpendicular to the tumor surface. TACS3 increases

    更新日期:2020-07-24
  • Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer.
    Cancer Metab. (IF 5.033) Pub Date : 2020-06-19
    Kaylyn D Tousignant,Anja Rockstroh,Berwyck L J Poad,Ali Talebi,Reuben S E Young,Atefeh Taherian Fard,Rajesh Gupta,Tuo Zang,Chenwei Wang,Melanie L Lehman,Johan V Swinnen,Stephen J Blanksby,Colleen C Nelson,Martin C Sadowski

    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

    更新日期:2020-07-24
  • PHGDH supports liver ceramide synthesis and sustains lipid homeostasis.
    Cancer Metab. (IF 5.033) Pub Date : 2020-06-15
    Yun Pyo Kang,Aimee Falzone,Min Liu,Paloma González-Sánchez,Bo-Hyun Choi,Jonathan L Coloff,James J Saller,Florian A Karreth,Gina M DeNicola

    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. To study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA

    更新日期:2020-07-24
  • Modulating pyrimidine ribonucleotide levels for the treatment of cancer
    Cancer Metab. (IF 5.033) Pub Date : 2020-06-09
    Tanzina Mollick; Sonia Laín

    By providing the necessary building blocks for nucleic acids and precursors for cell membrane synthesis, pyrimidine ribonucleotides are essential for cell growth and proliferation. Therefore, depleting pyrimidine ribonucleotide pools has long been considered as a strategy to reduce cancer cell growth. Here, we review the pharmacological approaches that have been employed to modulate pyrimidine ribonucleotide

    更新日期:2020-07-24
  • Common biochemical properties of metabolic genes recurrently dysregulated in tumors.
    Cancer Metab. (IF 5.033) Pub Date : 2020-05-08
    Krishnadev Oruganty,Scott Edward Campit,Sainath Mamde,Costas A Lyssiotis,Sriram Chandrasekaran

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

    更新日期:2020-05-08
  • Metabolic regulation of calcium pumps in pancreatic cancer: role of phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3).
    Cancer Metab. (IF 5.033) Pub Date : 2020-04-02
    D A Richardson,P Sritangos,A D James,A Sultan,J I E Bruce

    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

    更新日期:2020-04-02
  • Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma
    Cancer Metab. (IF 5.033) Pub Date : 2020-03-05
    L. Ren; V. Ruiz-Rodado; T. Dowdy; S. Huang; S. H. Issaq; J. Beck; H. Wang; C. Tran Hoang; A. Lita; M. Larion; A. K. LeBlanc

    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

    更新日期:2020-03-05
  • Metabolic models predict bacterial passengers in colorectal cancer.
    Cancer Metab. (IF 5.033) Pub Date : 2020-02-10
    Daniel R Garza,Rahwa Taddese,Jakob Wirbel,Georg Zeller,Annemarie Boleij,Martijn A Huynen,Bas E Dutilh

    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. Here, we investigate

    更新日期:2020-02-10
  • Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy.
    Cancer Metab. (IF 5.033) Pub Date : 2020-01-02
    Barbara S Nelson,Lin Lin,Daniel M Kremer,Cristovão M Sousa,Cecilia Cotta-Ramusino,Amy Myers,Johanna Ramos,Tina Gao,Ilya Kovalenko,Kari Wilder-Romans,Joseph Dresser,Mary Davis,Ho-Joon Lee,Zeribe C Nwosu,Scott Campit,Oksana Mashadova,Brandon N Nicolay,Zachary P Tolstyka,Christopher J Halbrook,Sriram Chandrasekaran,John M Asara,Howard C Crawford,Lewis C Cantley,Alec C Kimmelman,Daniel R Wahl,Costas A

    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. We utilized a doxycycline-inducible shRNA-mediated strategy to knockdown GOT1 in PDA and colorectal cancer

    更新日期:2020-01-02
  • Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells
    Cancer Metab. (IF 5.033) Pub Date : 2019-12-30
    Lei Yu; Shao Thing Teoh; Elliot Ensink; Martin P. Ogrodzinski; Che Yang; Ana I. Vazquez; Sophia Y. Lunt

    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

    更新日期:2019-12-30
  • A systematic flux analysis approach to identify metabolic vulnerabilities in human breast cancer cell lines
    Cancer Metab. (IF 5.033) Pub Date : 2019-12-27
    Sheree D. Martin; Sean L. McGee

    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

    更新日期:2019-12-27
  • HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells
    Cancer Metab. (IF 5.033) Pub Date : 2019-12-27
    Albertus T. J. Wierenga; Alan Cunningham; Ayşegül Erdem; Nuria Vilaplana Lopera; Annet Z. Brouwers-Vos; Maurien Pruis; André B. Mulder; Ulrich L. Günther; Joost H. A. Martens; Edo Vellenga; Jan Jacob Schuringa

    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. Genome-wide ChIPseq and

    更新日期:2019-12-27
  • SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia
    Cancer Metab. (IF 5.033) Pub Date : 2019-12-11
    Ali R. Nasiri; Marcos R. Rodrigues; Zongyu Li; Brooks P. Leitner; Rachel J. Perry

    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. E0771 breast tumors

    更新日期:2019-12-11
  • Molecular features that predict the response to antimetabolite chemotherapies.
    Cancer Metab. (IF 5.033) Pub Date : 2017-10-14
    Mahya Mehrmohamadi,Seong Ho Jeong,Jason W Locasale

    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

    更新日期:2019-11-01
  • Bortezomib resistance in multiple myeloma is associated with increased serine synthesis.
    Cancer Metab. (IF 5.033) Pub Date : 2017-09-01
    Esther A Zaal,Wei Wu,Gerrit Jansen,Sonja Zweegman,Jacqueline Cloos,Celia R Berkers

    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

    更新日期:2019-11-01
  • Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities.
    Cancer Metab. (IF 5.033) Pub Date : 2017-08-31
    Nathan J Lanning,Joshua P Castle,Simar J Singh,Andre N Leon,Elizabeth A Tovar,Amandeep Sanghera,Jeffrey P MacKeigan,Fabian V Filipp,Carrie R Graveel

    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

    更新日期:2019-11-01
  • HIF prolyl hydroxylase PHD3 regulates translational machinery and glucose metabolism in clear cell renal cell carcinoma.
    Cancer Metab. (IF 5.033) Pub Date : 2017-07-07
    Petra Miikkulainen,Heidi Högel,Krista Rantanen,Tomi Suomi,Petri Kouvonen,Laura L Elo,Panu M Jaakkola

    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

    更新日期:2019-11-01
  • 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. (IF 5.033) Pub Date : 2017-03-07
    Loreta M Rodrigues,Santiago Uribe-Lewis,Basetti Madhu,Davina J Honess,Marion Stubbs,John R Griffiths

    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. This "butyrate paradox" is thought to be due to butyrate mediating histone

    更新日期:2019-11-01
  • The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity.
    Cancer Metab. (IF 5.033) Pub Date : 2017-02-12
    Renaud Vatrinet,Giulia Leone,Monica De Luise,Giulia Girolimetti,Michele Vidone,Giuseppe Gasparre,Anna Maria Porcelli

    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

    更新日期:2019-11-01
  • Mitochondrial mutations and metabolic adaptation in pancreatic cancer.
    Cancer Metab. (IF 5.033) Pub Date : 2017-01-30
    Rae-Anne Hardie,Ellen van Dam,Mark Cowley,Ting-Li Han,Seher Balaban,Marina Pajic,Mark Pinese,Mary Iconomou,Robert F Shearer,Jessie McKenna,David Miller,Nicola Waddell,John V Pearson,Sean M Grimmond,,Leonid Sazanov,Andrew V Biankin,Silas Villas-Boas,Andrew J Hoy,Nigel Turner,Darren N Saunders

    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

    更新日期:2019-11-01
  • Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration.
    Cancer Metab. (IF 5.033) Pub Date : 2017-01-20
    Seher Balaban,Robert F Shearer,Lisa S Lee,Michelle van Geldermalsen,Mark Schreuder,Harrison C Shtein,Rose Cairns,Kristen C Thomas,Daniel J Fazakerley,Thomas Grewal,Jeff Holst,Darren N Saunders,Andrew J Hoy

    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

    更新日期:2019-11-01
  • The role of tumor metabolism as a driver of prostate cancer progression and lethal disease: results from a nested case-control study.
    Cancer Metab. (IF 5.033) Pub Date : 2016-12-17
    Rachel S Kelly,Jennifer A Sinnott,Jennifer R Rider,Ericka M Ebot,Travis Gerke,Michaela Bowden,Andreas Pettersson,Massimo Loda,Howard D Sesso,Philip W Kantoff,Neil E Martin,Edward L Giovannucci,Svitlana Tyekucheva,Matthew Vander Heiden,Lorelei A Mucci

    BACKGROUND Understanding the biologic mechanisms underlying the development of lethal prostate cancer is critical for improved therapeutic and prevention strategies. In this study we explored the role of tumor metabolism in prostate cancer progression using mRNA expression profiling of seven metabolic pathways; fatty acid metabolism, glycolysis/gluconeogenesis, oxidative phosphorylation, pentose phosphate

    更新日期:2019-11-01
  • Weight control interventions improve therapeutic efficacy of dacarbazine in melanoma by reversing obesity-induced drug resistance.
    Cancer Metab. (IF 5.033) Pub Date : 2016-12-17
    Parmanand Malvi,Balkrishna Chaube,Shivendra Vikram Singh,Naoshad Mohammad,Vimal Pandey,Maleppillil Vavachan Vijayakumar,Revathy Meenatheril Radhakrishnan,Muralidharan Vanuopadath,Sudarslal Sadasivan Nair,Bipin Gopalakrishnan Nair,Manoj Kumar Bhat

    BACKGROUND Obesity-related cellular, metabolic, and molecular alterations have been shown to increase cancer risk and tumor progression and are associated with poorer therapeutic outcome in cancer patients. However, the impact of obesity and weight-control interventions on the therapeutic response in melanoma is poorly understood. METHODS High fat diet (HFD)-induced obese mouse model was used in this

    更新日期:2019-11-01
  • Epithelial-mesenchymal transition induction is associated with augmented glucose uptake and lactate production in pancreatic ductal adenocarcinoma.
    Cancer Metab. (IF 5.033) Pub Date : 2016-10-26
    Menghan Liu,Lake-Ee Quek,Ghazal Sultani,Nigel Turner

    BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a common malignancy with dismal prognosis. Metastatic spread and therapeutic resistance, the main causes of PDAC-related mortalities, are both partially underlined by the epithelial-mesenchymal transition (EMT) of PDAC cells. While the role of Warburg metabolism has been recognized in supporting rapid cellular growth and proliferation in many cancer

    更新日期:2019-11-01
  • Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer.
    Cancer Metab. (IF 5.033) Pub Date : 2016-10-13
    Stephanie Sprowl-Tanio,Amber N Habowski,Kira T Pate,Miriam M McQuade,Kehui Wang,Robert A Edwards,Felix Grun,Yung Lyou,Marian L Waterman

    BACKGROUND There is increasing evidence that oncogenic Wnt signaling directs metabolic reprogramming of cancer cells to favor aerobic glycolysis or Warburg metabolism. In colon cancer, this reprogramming is due to direct regulation of pyruvate dehydrogenase kinase 1 (PDK1) gene transcription. Additional metabolism genes are sensitive to Wnt signaling and exhibit correlative expression with PDK1. Whether

    更新日期:2019-11-01
  • Starving cancer from the outside and inside: separate and combined effects of calorie restriction and autophagy inhibition on Ras-driven tumors.
    Cancer Metab. (IF 5.033) Pub Date : 2016-09-22
    Laura M Lashinger,Ciara H O'Flanagan,Sarah M Dunlap,Audrey J Rasmussen,Shannon Sweeney,Jessie Yangxiang Guo,Alessia Lodi,Stefano Tiziani,Eileen White,Stephen D Hursting

    BACKGROUND Calorie restriction (CR) prevents obesity and exerts anticancer effects in many preclinical models. CR is also increasingly being used in cancer patients as a sensitizing strategy prior to chemotherapy regimens. While the beneficial effects of CR are widely accepted, the mechanisms through which CR affects tumor growth are incompletely understood. In many cell types, CR and other nutrient

    更新日期:2019-11-01
  • A rapid method for quantifying free and bound acetate based on alkylation and GC-MS analysis.
    Cancer Metab. (IF 5.033) Pub Date : 2016-09-07
    Sergey Tumanov,Vinay Bulusu,Eyal Gottlieb,Jurre J Kamphorst

    BACKGROUND Acetyl-CoA is a key metabolic intermediate with roles in the production of energy and biomass, as well as in metabolic regulation. It was recently found that acetate is crucial for maintaining acetyl-CoA production in hypoxic cancer cells. However, the availability of free acetate in the tumor environment and how much tumor cells consume remains unknown. Similarly, much is still to be learned

    更新日期:2019-11-01
  • Metabolic requirements for cancer cell proliferation.
    Cancer Metab. (IF 5.033) Pub Date : 2016-08-20
    Mark A Keibler,Thomas M Wasylenko,Joanne K Kelleher,Othon Iliopoulos,Matthew G Vander Heiden,Gregory Stephanopoulos

    BACKGROUND The study of cancer metabolism has been largely dedicated to exploring the hypothesis that oncogenic transformation rewires cellular metabolism to sustain elevated rates of growth and division. Intense examination of tumors and cancer cell lines has confirmed that many cancer-associated metabolic phenotypes allow robust growth and survival; however, little attention has been given to explicitly

    更新日期:2019-11-01
  • Malonate as a ROS product is associated with pyruvate carboxylase activity in acute myeloid leukaemia cells.
    Cancer Metab. (IF 5.033) Pub Date : 2016-08-06
    Michelle A C Reed,Christian Ludwig,Christopher M Bunce,Farhat L Khanim,Ulrich L Günther

    BACKGROUND The role of anaplerotic nutrient entry into the Krebs cycle via pyruvate carboxylase has been the subject of increased scrutiny and in particular whether this is dysregulated in cancer. Here, we use a tracer-based NMR analysis involving high-resolution (1)H-(13)C-HSQC spectra to assess site-specific label incorporation into a range of metabolite pools, including malate, aspartate and glutamate

    更新日期:2019-11-01
  • Novel drugs that target the metabolic reprogramming in renal cell cancer.
    Cancer Metab. (IF 5.033) Pub Date : 2016-07-16
    Johannes C van der Mijn,David J Panka,Andrew K Geissler,Henk M Verheul,James W Mier

    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

    更新日期:2019-11-01
  • 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.
    Cancer Metab. (IF 5.033) Pub Date : 2016-07-06
    Lake-Ee Quek,Menghan Liu,Sanket Joshi,Nigel Turner

    BACKGROUND Glucose and glutamine are the two dominant metabolic substrates in cancer cells. In (13)C tracer experiments, however, it is necessary to account for all significant input substrates, as some natural (unlabelled) substrate in the medium, often derived from serum, can be metabolised by cells despite not showing signs of net consumption. RESULTS Using [U-(13)C6]-glucose tracers and measuring

    更新日期:2019-11-01
  • Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes.
    Cancer Metab. (IF 5.033) Pub Date : 2016-06-29
    Tonje H Haukaas,Leslie R Euceda,Guro F Giskeødegård,Santosh Lamichhane,Marit Krohn,Sandra Jernström,Miriam R Aure,Ole C Lingjærde,Ellen Schlichting,Øystein Garred,Eldri U Due,Gordon B Mills,Kristine K Sahlberg,Anne-Lise Børresen-Dale,Tone F Bathen,

    BACKGROUND The heterogeneous biology of breast cancer leads to high diversity in prognosis and response to treatment, even for patients with similar clinical diagnosis, histology, and stage of disease. Identifying mechanisms contributing to this heterogeneity may reveal new cancer targets or clinically relevant subgroups for treatment stratification. In this study, we have merged metabolite, protein

    更新日期:2019-11-01
  • Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool.
    Cancer Metab. (IF 5.033) Pub Date : 2016-06-09
    Dustin G Brown,Sangeeta Rao,Tiffany L Weir,Joanne O'Malia,Marlon Bazan,Regina J Brown,Elizabeth P Ryan

    BACKGROUND Colorectal cancers (CRC) are associated with perturbations in cellular amino acids, nucleotides, pentose-phosphate pathway carbohydrates, and glycolytic, gluconeogenic, and tricarboxylic acid intermediates. A non-targeted global metabolome approach was utilized for exploring human CRC, adjacent mucosa, and stool. In this pilot study, we identified metabolite profile differences between CRC

    更新日期:2019-11-01
  • Molecular characterization of Gleason patterns 3 and 4 prostate cancer using reverse Warburg effect-associated genes.
    Cancer Metab. (IF 5.033) Pub Date : 2016-05-07
    Ilinca Georgescu,Robert J Gooding,R Christopher Doiron,Andrew Day,Shamini Selvarajah,Chris Davidson,David M Berman,Paul C Park

    BACKGROUND Gleason scores (GS) 3+3 and 3+4 prostate cancers (PCa) differ greatly in their clinical courses, with Gleason pattern (GP) 4 representing a major independent risk factor for cancer progression. However, Gleason grade is not reliably ascertained by diagnostic biopsy, largely due to sampling inadequacies, subjectivity in the Gleason grading procedure, and a lack of more objective biomarker

    更新日期:2019-11-01
  • Metabolic changes associated with methionine stress sensitivity in MDA-MB-468 breast cancer cells.
    Cancer Metab. (IF 5.033) Pub Date : 2016-05-04
    Stacey L Borrego,Johannes Fahrmann,Rupsa Datta,Chiara Stringari,Dmitry Grapov,Michael Zeller,Yumay Chen,Ping Wang,Pierre Baldi,Enrico Gratton,Oliver Fiehn,Peter Kaiser

    BACKGROUND The majority of cancer cells have a unique metabolic requirement for methionine that is not observed in normal, non-tumorigenic cells. This phenotype is described as "methionine dependence" or "methionine stress sensitivity" in which cancer cells are unable to proliferate when methionine has been replaced with its metabolic precursor, homocysteine, in cell culture growth media. We focus

    更新日期:2019-11-01
  • Bridging the gap between non-targeted stable isotope labeling and metabolic flux analysis.
    Cancer Metab. (IF 5.033) Pub Date : 2016-04-26
    Daniel Weindl,Thekla Cordes,Nadia Battello,Sean C Sapcariu,Xiangyi Dong,Andre Wegner,Karsten Hiller

    BACKGROUND Metabolism gained increasing interest for the understanding of diseases and to pinpoint therapeutic intervention points. However, classical metabolomics techniques only provide a very static view on metabolism. Metabolic flux analysis methods, on the other hand, are highly targeted and require detailed knowledge on metabolism beforehand. RESULTS We present a novel workflow to analyze non-targeted

    更新日期:2019-11-01
  • Pre-diagnosis blood glucose and prognosis in women with breast cancer.
    Cancer Metab. (IF 5.033) Pub Date : 2016-04-08
    Behjatolah Monzavi-Karbassi,Rhonda Gentry,Varinder Kaur,Eric R Siegel,Fariba Jousheghany,Srikanth Medarametla,Barbara J Fuhrman,A Mazin Safar,Laura F Hutchins,Thomas Kieber-Emmons

    BACKGROUND The effect of moderately elevated blood glucose levels among non-diabetic subjects on cancer prognosis is not well described. The goal of this study was to examine the association of elevated random blood glucose (RBG) levels in non-diabetic breast cancer patients with overall survival (OS) and time to tumor recurrence (TTR). RESULTS Forty-nine deaths and 32 recurrences occurred among 148

    更新日期:2019-11-01
  • Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments.
    Cancer Metab. (IF 5.033) Pub Date : 2016-04-05
    Barrie Peck,Zachary T Schug,Qifeng Zhang,Beatrice Dankworth,Dylan T Jones,Elizabeth Smethurst,Rachana Patel,Susan Mason,Ming Jiang,Rebecca Saunders,Michael Howell,Richard Mitter,Bradley Spencer-Dene,Gordon Stamp,Lynn McGarry,Daniel James,Emma Shanks,Eric O Aboagye,Susan E Critchlow,Hing Y Leung,Adrian L Harris,Michael J O Wakelam,Eyal Gottlieb,Almut Schulze

    BACKGROUND Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. RESULTS Using functional genomics, we identified stearoyl-CoA desaturase

    更新日期:2019-11-01
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  • Warburg effect(s)-a biographical sketch of Otto Warburg and his impacts on tumor metabolism.
    Cancer Metab. (IF 5.033) Pub Date : 2016-03-11
    Angela M Otto

    Virtually everyone working in cancer research is familiar with the "Warburg effect", i.e., anaerobic glycolysis in the presence of oxygen in tumor cells. However, few people nowadays are aware of what lead Otto Warburg to the discovery of this observation and how his other scientific contributions are seminal to our present knowledge of metabolic and energetic processes in cells. Since science is a

    更新日期:2019-11-01
  • Integration of omics: more than the sum of its parts.
    Cancer Metab. (IF 5.033) Pub Date : 2016-02-24
    Joerg Martin Buescher,Edward M Driggers

    Genome scale data on biological systems has increasingly become available by sequencing of DNA and RNA, and by mass spectrometric quantification of proteins and metabolites. The cellular components from which these -omics regimes are derived act as one integrated system in vivo; thus, there is a natural instinct to integrate -omics data types. Statistical analyses, the use of previous knowledge in

    更新日期:2019-11-01
  • The role of HIF-1 in oncostatin M-dependent metabolic reprogramming of hepatic cells.
    Cancer Metab. (IF 5.033) Pub Date : 2016-02-19
    Nadia Battello,Andreas David Zimmer,Carole Goebel,Xiangyi Dong,Iris Behrmann,Claude Haan,Karsten Hiller,Andre Wegner

    BACKGROUND Hypoxia and inflammation have been identified as hallmarks of cancer. A majority of hepatocellular carcinomas are preceded by hepatitis B- or C-related chronic infections suggesting that liver cancer development is promoted by an inflammatory microenvironment. The inflammatory cytokine oncostatin M (OSM) was shown to induce the expression of hypoxia-inducible factor-1 α (HIF-1 α) under normoxic

    更新日期:2019-11-01
  • Mathematical models of cancer metabolism.
    Cancer Metab. (IF 5.033) Pub Date : 2015-12-25
    Elke Katrin Markert,Alexei Vazquez

    Metabolism is essential for life, and its alteration is implicated in multiple human diseases. The transformation from a normal to a cancerous cell requires metabolic changes to fuel the high metabolic demands of cancer cells, including but not limited to cell proliferation and cell migration. In recent years, there have been a number of new discoveries connecting known aberrations in oncogenic and

    更新日期:2019-11-01
  • Evidence that 2-hydroxyglutarate is not readily metabolized in colorectal carcinoma cells.
    Cancer Metab. (IF 5.033) Pub Date : 2015-12-03
    Susan J Gelman,Nathaniel G Mahieu,Kevin Cho,Elizabeth M Llufrio,Timothy A Wencewicz,Gary J Patti

    BACKGROUND Two-hydroxyglutarate (2HG) is present at low concentrations in healthy mammalian cells as both an L and D enantiomer. Both the L and D enantiomers have been implicated in regulating cellular physiology by mechanisms that are only partially characterized. In multiple human cancers, the D enantiomer accumulates due to gain-of-function mutations in the enzyme isocitrate dehydrogenase (IDH)

    更新日期:2019-11-01
  • Targeting mitochondrial complex I using BAY 87-2243 reduces melanoma tumor growth.
    Cancer Metab. (IF 5.033) Pub Date : 2015-10-27
    Laura Schöckel,Andrea Glasauer,Farhan Basit,Katharina Bitschar,Hoa Truong,Gerrit Erdmann,Carolyn Algire,Andrea Hägebarth,Peter Hgm Willems,Charlotte Kopitz,Werner Jh Koopman,Mélanie Héroult

    BACKGROUND Numerous studies have demonstrated that functional mitochondria are required for tumorigenesis, suggesting that mitochondrial oxidative phosphorylation (OXPHOS) might be a potential target for cancer therapy. In this study, we investigated the effects of BAY 87-2243, a small molecule that inhibits the first OXPHOS enzyme (complex I), in melanoma in vitro and in vivo. RESULTS BAY 87-2243

    更新日期:2019-11-01
  • Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by ß-lapachone.
    Cancer Metab. (IF 5.033) Pub Date : 2015-10-16
    Gaurab Chakrabarti,Zachary R Moore,Xiuquan Luo,Mariya Ilcheva,Aktar Ali,Mahesh Padanad,Yunyun Zhou,Yang Xie,Sandeep Burma,Pier P Scaglioni,Lewis C Cantley,Ralph J DeBerardinis,Alec C Kimmelman,Costas A Lyssiotis,David A Boothman

    BACKGROUND Pancreatic ductal adenocarcinomas (PDA) activate a glutamine-dependent pathway of cytosolic nicotinamide adenine dinucleotide phosphate (NADPH) production to maintain redox homeostasis and support proliferation. Enzymes involved in this pathway (GLS1 (mitochondrial glutaminase 1), GOT1 (cytoplasmic glutamate oxaloacetate transaminase 1), and GOT2 (mitochondrial glutamate oxaloacetate transaminase