Cancer metabolism

  • Article
    | Open Access

    Cancer cells need to reprogramme their metabolism to allow rapid cell proliferation. Here, the authors show that USP13is amplified in ovarian cancer and its protein product, a deubiquitinase, drives tumour progression by rewiring the metabolism of cancer cells by stabilising two critical metabolic enzymes.

    • Cecil Han
    • , Lifeng Yang
    •  & Xiongbin Lu
  • Article
    | Open Access

    Cancer cells reprogramme their metabolism with unclear clinical implications. Here, the authors analyse the expression of metabolic genes across 20 types of solid cancers and find that clinical aggressiveness, poor survival and metastasis are associated with the deregulation of mitochondrial metabolism.

    • Edoardo Gaude
    •  & Christian Frezza
  • Article
    | Open Access

    Oncogenic mutations of isocitrate dehydrogenases 1 and 2 result in the production of the oncometabolite R-2-hydroxyglutarate. Here the authors show that the oncometabolite promotes mTOR activation in a PTEN/PI3K-independent manner by regulating DEPTOR stability via inhibition of KDM4A activity.

    • Mélissa Carbonneau
    • , Laurence M. Gagné
    •  & Frédérick A. Mallette
  • Article
    | Open Access

    Chemerin is an adipokine often downregulated in tumours. Here the authors show that chemotherapy induces chemerin production by endothelial cells, leading to cachexia, and that VEGF ablation in myeloid cells prevents cachexia in a chemerin-dependent manner, and improves chemotherapeutic effects.

    • Ralph Klose
    • , Ewelina Krzywinska
    •  & Christian Stockmann
  • Article
    | Open Access

    In conditions of energy stress cells reduce transcription of ribosomal RNA (rRNA) to maintain cell survival. Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.

    • Lianhui Sun
    • , Guangjian Fan
    •  & Chuangui Wang
  • Article
    | Open Access

    Protein phosphatase Cdc25 controls cell cycle transitions by dephosphorylating CDK substrates. Here, the authors show that the Cdc25A isoform regulates glycolysis through dephosphorylation of pyruvate kinase PKM2, resulting in β-catenin activation and consequent upregulation of the transcription of glycolytic genes.

    • Ji Liang
    • , Ruixiu Cao
    •  & Zhimin Lu
  • Article
    | Open Access

    Tumour hypoxia reduces the efficacy of radiotherapy. Starting from a drug screen, here the authors demonstrate that the anti-malarial, atovaquone, reduces the oxygen consumption rate of cancer cells by inhibition of mitochondrial complex III and sensitises to radiotherapy by reducing tumour hypoxia.

    • Thomas M. Ashton
    • , Emmanouil Fokas
    •  & William Gillies McKenna
  • Article
    | Open Access

    Viruses can reprogram glutamine metabolism of host cells to support bioenergetics demands of viral replication. Here the authors show that adenoviral infection leads to enhanced glutamine metabolism through virus-mediated activation of MYC, which is required for optimal progeny virion generation.

    • Minh Thai
    • , Shivani K. Thaker
    •  & Heather R. Christofk
  • Article
    | Open Access

    The pentose phosphate pathway is aberrantly activated in cancer cells but the mechanism is unclear. Here, the authors show that G6PD, the rate-limiting enzyme in the pathway, is post-translationally modified with a sugar moiety under hypoxic conditions leading to increased production of precursors for macromolecular synthesis and antioxidants.

    • Xiongjian Rao
    • , Xiaotao Duan
    •  & Wen Yi
  • Article
    | Open Access

    Tumour cells can survive by evading cell death pathways and altering their metabolism to adapt to their local environment. In this study, Iansanteet al. show that the anti-apoptotic protein PARP14 maintains low PKM2 activity, leading to enhanced glycolysis, demonstrating a link between suppression of apoptosis and altered metabolism.

    • Valeria Iansante
    • , Pui Man Choy
    •  & Salvatore Papa
  • Article |

    The transcription factor c-Myc is a master regulator of cellular metabolism and has an important role in tumorigenesis. Phanet al. show that 14-3-3σ, an inhibitor of cell cycle progression, also suppresses tumour-promoting metabolic programmes by promoting the degradation of c-Myc.

    • Liem Phan
    • , Ping-Chieh Chou
    •  & Mong-Hong Lee
  • Article |

    The RNA-binding proteins Lin28A and Lin28B are known to have key roles in a variety of pathological states including cancer, obesity and diabetes. Here the authors show that Lin28A and -B alter cancer metabolism through let-7-mediated upregulation of pyruvate dehydrogenase kinase 1.

    • Xiaoyu Ma
    • , Chenchen Li
    •  & Huafeng Zhang
  • Article
    | Open Access

    Defective proteins or functional proteins that are no longer needed can be degraded in the endoplasmic reticulum. In this study, Lopez-Serra et al.show that DERL3, which is involved in protein degradation in the endoplasmic reticulum, is aberrantly silenced in cancer, leading to activation of a glucose transporter and dysregulated glycolysis.

    • Paula Lopez-Serra
    • , Miguel Marcilla
    •  & Manel Esteller
  • Article |

    Cellular metabolism is dysregulated in cancer and may be reflected in differences in the expression of metabolic genes. In this study, the authors find that mitochondrial folate-coupled dehydrogenase is increased in expression in a wide variety of cancers and negatively correlates with breast cancer patient survival.

    • Roland Nilsson
    • , Mohit Jain
    •  & Vamsi K. Mootha
  • Article |

    Many cancers harbour mutations in the tumour suppressor p53, which often then gains oncogenic functions. Here, the authors show that mutant p53 enhances glycolysis in tumour cells by promoting glucose uptake via a mechanism involving GLUT1, RhoA and ROCK.

    • Cen Zhang
    • , Juan Liu
    •  & Zhaohui Feng
  • Article |

    The metabolic reaction catalysed by the isocitrate dehydrogenase 1 (IDH1) enzyme is commonly perturbed in some glioma subtypes due to gain-of-function mutations in the IDH1 gene. Here, Chaumeil et al.present a method that detects mutant IDH1 activity by measuring the levels of different hyperpolarized metabolites produced by wild-type and mutant IDH1.

    • Myriam M. Chaumeil
    • , Peder E. Z. Larson
    •  & Sabrina M. Ronen
  • Article |

    Tumour cells utilize a pool of the molecular chaperone heat shock protein 90 to ensure correct protein folding in mitochondria. Here, the authors demonstrate that mitochondrial heat shock protein 90 regulates the folding of a subunit of the electron transport chain and that this can contribute to tumorigenesis.

    • Young Chan Chae
    • , Alessia Angelin
    •  & Dario C. Altieri