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Article
| Open Access
Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
A screen of nutrient-derived compounds identified trans-vaccenic acid as a promoter of effector T cell function, and functional assays demonstrate that this occurs via inactivation of GPR43 on T cells.
- Hao Fan
- , Siyuan Xia
- & Jing Chen
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Article |
Disruption of sugar nucleotide clearance is a therapeutic vulnerability of cancer cells
An enzyme called UXS1 that converts one sugar nucleotide to another is needed more in some cancer cells than in normal cells, providing a potential weakness that can be exploited therapeutically.
- Mihir B. Doshi
- , Namgyu Lee
- & Dohoon Kim
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Article |
CRISPR screens decode cancer cell pathways that trigger γδ T cell detection
A combination of genome-wide CRISPR screens in target cancer cells identifies pathways that regulate γδ T cell killing and BTN3A cell surface expression.
- Murad R. Mamedov
- , Shane Vedova
- & Alexander Marson
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Matters Arising |
Reply to: DHODH inhibitors sensitize to ferroptosis by FSP1 inhibition
- Chao Mao
- , Xiaoguang Liu
- & Boyi Gan
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Article |
Tumour extracellular vesicles and particles induce liver metabolic dysfunction
Remote tumours cause liver dysfunction by releasing extracellular vesicles and particles containing palmitic acid, which induces TNF signalling in Kupffer cells, resulting in inflammation, fatty deposits and metabolic dysregulation, thus both reducing the efficacy and increasing the toxicity of chemotherapies.
- Gang Wang
- , Jianlong Li
- & David Lyden
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Article
| Open Access
Uridine-derived ribose fuels glucose-restricted pancreatic cancer
A metabolite screen of pancreatic cells shows that pancreatic cancer cells metabolize uridine-derived ribose via UPP1, supporting redox balance, survival and proliferation.
- Zeribe C. Nwosu
- , Matthew H. Ward
- & Costas A. Lyssiotis
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Article |
Slow TCA flux and ATP production in primary solid tumours but not metastases
As solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.
- Caroline R. Bartman
- , Daniel R. Weilandt
- & Joshua D. Rabinowitz
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Article
| Open Access
Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome
Cleaved and intact type I collagen have different effects on pancreatic ductal adenocarcinoma (PDAC), and remodelling of type I collagen—mediated through DDR1 signalling—is a prognostic indicator for the survival of patients with PDAC.
- Hua Su
- , Fei Yang
- & Michael Karin
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Article
| Open Access
Brown-fat-mediated tumour suppression by cold-altered global metabolism
Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.
- Takahiro Seki
- , Yunlong Yang
- & Yihai Cao
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Article
| Open Access
PI3K drives the de novo synthesis of coenzyme A from vitamin B5
The PI3K–PANK4 axis regulates coenzyme A synthesis, the abundance of acetyl-CoA, and CoA-dependent processes such as lipid metabolism, and these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone and growth-factor-driven or oncogene-driven metabolism and growth.
- Christian C. Dibble
- , Samuel A. Barritt
- & Alex Toker
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Article |
PHGDH heterogeneity potentiates cancer cell dissemination and metastasis
PHDGH heterogeneity in primary tumours could be a sign of tumour aggressiveness.
- Matteo Rossi
- , Patricia Altea-Manzano
- & Sarah-Maria Fendt
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Article |
β-Hydroxybutyrate suppresses colorectal cancer
The growth of colorectal cancer is reduced by ketogenic diet consumption, the properties of which are mediated by the ketone body β-hydroxybutyrate.
- Oxana Dmitrieva-Posocco
- , Andrea C. Wong
- & Maayan Levy
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Article |
A non-canonical tricarboxylic acid cycle underlies cellular identity
A non-canonical tricarboxylic acid cycle is required for changes in cell state.
- Paige K. Arnold
- , Benjamin T. Jackson
- & Lydia W. S. Finley
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Article |
SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells
SLC25A39 and its paralogue SLC25A40 have redundant roles in the import of glutathione into mitochondria of mammalian cells.
- Ying Wang
- , Frederick S. Yen
- & Kıvanç Birsoy
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Article |
Low glycaemic diets alter lipid metabolism to influence tumour growth
Lien et al. show that low glycemic diets can reduce tumour growth by deregulating lipid metabolism.
- Evan C. Lien
- , Anna M. Westermark
- & Matthew G. Vander Heiden
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Article |
Dietary fructose improves intestinal cell survival and nutrient absorption
A high-fructose diet in mice improves the survival of intestinal epithelial cells, which leads to an increase in gut surface area, enhanced absorption of lipids and the promotion of tumour growth and obesity.
- Samuel R. Taylor
- , Shakti Ramsamooj
- & Marcus D. Goncalves
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Article |
DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer
DHO dehydrogenase regulates ferroptosis by preventing mitochondrial lipid peroxidation and its inhibition suppresses growth in tumours with low levels of GPX4.
- Chao Mao
- , Xiaoguang Liu
- & Boyi Gan
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Article |
Cell-programmed nutrient partitioning in the tumour microenvironment
Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells.
- Bradley I. Reinfeld
- , Matthew Z. Madden
- & W. Kimryn Rathmell
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Article |
CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours
CTLA-4 promotes glucose uptake by tumour-infiltrating regulatory T cells, making them unstable.
- Roberta Zappasodi
- , Inna Serganova
- & Taha Merghoub
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Article |
Plasticity of ether lipids promotes ferroptosis susceptibility and evasion
The cellular organelles peroxisomes contribute to the sensitivity of cells to ferroptosis by synthesizing polyunsaturated ether phospholipids, and changes in the abundances of these lipids are associated with altered sensitivity to ferroptosis during cell-state transitions.
- Yilong Zou
- , Whitney S. Henry
- & Stuart L. Schreiber
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Article |
Cancer SLC43A2 alters T cell methionine metabolism and histone methylation
Expression of the transporter SLC43A2 by tumour cells allows them to outcompete T cells for methionine and thereby disrupt the survival and function of tumour-infiltrating T cells.
- Yingjie Bian
- , Wei Li
- & Weiping Zou
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Article |
Age-induced accumulation of methylmalonic acid promotes tumour progression
Ageing in humans is associated with an increase in circulating methylmalonic acid, which induces expression of SOX4 and promotes tumour progression.
- Ana P. Gomes
- , Didem Ilter
- & John Blenis
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Article |
Serine restriction alters sphingolipid diversity to constrain tumour growth
In xenograft tumour models in mice, modulation of dietary serine, serine palmitoyltransferase or phosphoglycerate dehydrogenase activity enables control of the endogenous synthesis of deoxysphingolipids, sensitizing the tumours to metabolic stress and slowing their progression.
- Thangaselvam Muthusamy
- , Thekla Cordes
- & Christian M. Metallo
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Article |
Fasting-mimicking diet and hormone therapy induce breast cancer regression
In mice, periodic fasting or a fasting-mimicking diet enhances the efficacy of endocrine therapy for breast cancer and delays acquired resistance to it; in patients with breast cancer, a fasting-mimicking diet recreates the metabolic changes observed in mice.
- Irene Caffa
- , Vanessa Spagnolo
- & Alessio Nencioni
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Article |
Mitochondrial ubiquinol oxidation is necessary for tumour growth
Oxidation of ubiquinol by the mitochondrial electron transfer chain drives tumour growth by maintaining the function of the oxidative Krebs cycle and de novo pyrimidine synthesis.
- Inmaculada Martínez-Reyes
- , Luzivette Robles Cardona
- & Navdeep S. Chandel
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Article |
Oncometabolites suppress DNA repair by disrupting local chromatin signalling
Metabolites that are elevated in tumours inhibit the lysine demethylase KDM4B, resulting in aberrant hypermethylation of histone 3 lysine 9 and decreased homology-dependent DNA repair.
- Parker L. Sulkowski
- , Sebastian Oeck
- & Peter M. Glazer
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Article |
Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I
Inhibition of the autophagy–lysosome system upregulates surface expression of MHC class I proteins and enhances antigen presentation, and evokes a potent anti-tumour immune response that is mediated by CD8+ T cells.
- Keisuke Yamamoto
- , Anthony Venida
- & Alec C. Kimmelman
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Review Article |
Dietary modifications for enhanced cancer therapy
- Naama Kanarek
- , Boryana Petrova
- & David M. Sabatini
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Article |
Mechanical regulation of glycolysis via cytoskeleton architecture
Glycolysis in normal epithelial cells responds to microenvironmental mechanics via the modulation of actin bundles that sequester the phosphofructokinase-targeting ubiquitin ligase TRIM21, a process superseded by persistent actin bundles in cancer cells.
- Jin Suk Park
- , Christoph J. Burckhardt
- & Gaudenz Danuser
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Article |
KRAS4A directly regulates hexokinase 1
KRAS4A interacts directly with hexokinase 1 in a GTP-dependent manner at the outer mitochondrial membrane, leading to kinase activation and an increase in glucose uptake and glycolysis in tumour cells.
- Caroline R. Amendola
- , James P. Mahaffey
- & Mark R. Philips
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Article |
In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer
A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells.
- Milica Momcilovic
- , Anthony Jones
- & David B. Shackelford
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Article |
Metabolic regulation of gene expression by histone lactylation
The lactylation of lysine residues on histones in mammalian cells is stimulated by hypoxia and bacterial challenges, and increased histone lactylation induces genes involved in wound healing.
- Di Zhang
- , Zhanyun Tang
- & Yingming Zhao
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Article |
The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
A synthetic lethal CRISPR–Cas9 screen identifies ferroptosis suppressor protein 1 as a key ferroptosis-resistance factor, the expression of which correlates with ferroptosis resistance in hundreds of cancer cell lines.
- Kirill Bersuker
- , Joseph M. Hendricks
- & James A. Olzmann
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Letter |
α-Ketoglutarate links p53 to cell fate during tumour suppression
Restoring the function of p53 in a mouse model of pancreatic ductal adenocarcinoma leads to the accumulation of α-ketoglutarate, which increases levels of the 5-hydroxymethylcytosine chromatin modification and results in reduced tumour-cell fitness.
- John P. Morris IV
- , Jossie J. Yashinskie
- & Scott W. Lowe
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Letter |
Dietary methionine influences therapy in mouse cancer models and alters human metabolism
In two patient-derived xenograft models of colorectal cancer and a mouse model of autochthonous soft-tissue sarcoma, dietary restriction of methionine influences the outcome of cancer and interacts with antimetabolite and radiation therapies, through effects on one-carbon metabolism.
- Xia Gao
- , Sydney M. Sanderson
- & Jason W. Locasale
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Letter |
UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis
UDP-glucose has a tumour-suppressive role by inhibiting the association between HuR and SNAI1 mRNA, whereas UGDH-mediated metabolism of UDP-glucose leads to increased SNAI1 mRNA stability and expression, thereby promoting tumour cell migration and lung cancer metastasis.
- Xiongjun Wang
- , Ruilong Liu
- & Weiwei Yang
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Letter |
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts
The authors find that stromal methyltransferase nicotinamide N-methyltransferase (NNMT) regulates the transition of normal fibroblasts to cancer-associated fibroblasts through histone methylation and promotes ovarian cancer growth and metastasis.
- Mark A. Eckert
- , Fabian Coscia
- & Ernst Lengyel
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Letter |
CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
Interferon-γ induces ferroptotic cell death in tumours by suppressing cystine uptake and promoting lipid peroxidation.
- Weimin Wang
- , Michael Green
- & Weiping Zou
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Letter |
NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling
NAD metabolic pathway choice in cancer is largely dependent on the tissue of origin, with implications for the development of precision treatments.
- Sudhir Chowdhry
- , Ciro Zanca
- & Paul S. Mischel
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Letter |
LLGL2 rescues nutrient stress by promoting leucine uptake in ER+ breast cancer
The polarity protein LLGL2 supports tumour growth in breast cancer by promoting leucine uptake and adaptation to nutrient stress.
- Yasuhiro Saito
- , Lewyn Li
- & Senthil K. Muthuswamy
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Letter |
Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle
Crystal structures of ATP citrate lyase from bacteria, archaea and humans unravel how the enzyme directs the formation of the central metabolite acetyl-CoA, and shed light onto the evolutionary origins of the Krebs cycle.
- Koen H. G. Verschueren
- , Clement Blanchet
- & Kenneth Verstraete
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Letter |
Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism
The transcription factor BACH1, which targets mitochondrial metabolism, is expressed at high levels in several types of cancer; reducing its expression in tumours makes them more susceptible to treatment with mitochondrial inhibitors.
- Jiyoung Lee
- , Ali E. Yesilkanal
- & Marsha Rich Rosner
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Article |
Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma
Gboxin and its chemical derivatives inhibit the growth of primary human and mouse glioblastoma cells, but not of mouse embryonic fibroblasts or neonatal astrocytes, by targeting mitochondrial oxidative phosphorylation complexes.
- Yufeng Shi
- , S. Kyun Lim
- & Luis F. Parada
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Letter |
Breast cancer cells rely on environmental pyruvate to shape the metastatic niche
Exogenous pyruvate is needed for breast cancer cells to form metastases, and the inhibition of pyruvate metabolism impairs collagen hydroxylation and the growth of lung metastases in different mouse models.
- Ilaria Elia
- , Matteo Rossi
- & Sarah-Maria Fendt
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Letter |
Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death
The authors find that loss of squalene monooxygenase expression alters the lipid metabolism of cancer cells, which confers protection from ferroptotic cell death and thus promotes tumour growth.
- Javier Garcia-Bermudez
- , Lou Baudrier
- & Kıvanç Birsoy
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Letter |
Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity
In several human and mouse cancer cell lines and carcinomas, a sapienate biosynthesis pathway underpins metabolic plasticity by allowing these cells to bypass stearoyl-CoA desaturase-dependent fatty acid desaturation.
- Kim Vriens
- , Stefan Christen
- & Sarah-Maria Fendt
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Letter |
Mannose impairs tumour growth and enhances chemotherapy
Mannose reduces the growth of tumour cells by impairing the metabolism of glucose, and enhances cell death when used in combination with conventional chemotherapy.
- Pablo Sierra Gonzalez
- , James O’Prey
- & Kevin M. Ryan
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Letter |
Autophagy maintains tumour growth through circulating arginine
Mice with whole-body or liver-specific deletion of Atg7 release circulating arginase I and have reduced levels of serum arginine, which impairs the growth of allografted arginine-auxotrophic tumours.
- Laura Poillet-Perez
- , Xiaoqi Xie
- & Eileen White
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Letter |
Histidine catabolism is a major determinant of methotrexate sensitivity
Histidine metabolism influences the sensitivity of cancer cells to methotrexate, with mice bearing leukaemia xenografts showing increased response to the drug upon histidine supplementation.
- Naama Kanarek
- , Heather R. Keys
- & David M. Sabatini
7-Dehydrocholesterol is an endogenous suppressor of ferroptosis