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Cellular and Molecular Life Sciences

, Volume 73, Issue 7, pp 1349–1363 | Cite as

Metabolic changes associated with tumor metastasis, part 2: Mitochondria, lipid and amino acid metabolism

  • Paolo E. Porporato
  • Valéry L. Payen
  • Bjorn Baselet
  • Pierre Sonveaux
Review

Abstract

Metabolic alterations are a hallmark of cancer controlling tumor progression and metastasis. Among the various metabolic phenotypes encountered in tumors, this review focuses on the contributions of mitochondria, lipid and amino acid metabolism to the metastatic process. Tumor cells require functional mitochondria to grow, proliferate and metastasize, but shifts in mitochondrial activities confer pro-metastatic traits encompassing increased production of mitochondrial reactive oxygen species (mtROS), enhanced resistance to apoptosis and the increased or de novo production of metabolic intermediates of the TCA cycle behaving as oncometabolites, including succinate, fumarate, and d-2-hydroxyglutarate that control energy production, biosynthesis and the redox state. Lipid metabolism and the metabolism of amino acids, such as glutamine, glutamate and proline are also currently emerging as focal control points of cancer metastasis.

Keywords

Tumor metastasis Oxidative phosphorylation (OXPHOS) Electron transport chain (ETC) Reactive oxygen species (ROS) Tricarboxylic acid cycle (TCA cycle)  Lipogenesis Glutaminolysis Proline metabolism 

Abbreviations

αKG

α-Ketoglutarate

Aco

Aconitase

ACLY

ATP-citrate lyase

CoA

Coenzyme A

CS

Citrate synthase

d-2HG

d-2-Hydroxyglutarate

EMT

Epithelial-to-mesenchymal transition

ETC

Electron transport chain

eSC

Embryonic stem cell

FASN

Fatty acid synthase

FH

Fumarate hydratase

GDH

Glutamate dehydrogenase

GLS

Glutaminase

HGFR

Hepatocyte growth factor receptor

HIF-1

Hypoxia-inducible factor-1

IDH

Isocitrate dehydrogenase

KEAP1

Kelch-like ECH-associated protein 1

KRAS

Kirsten Rat Sarcoma

MCL-1

Myeloid cell leukemia-1

mtROS

Mitochondrial reactive oxygen species

mTORC1

Mammalian target of rapamycin complex 1

NF-κB

Nuclear factor-κB

NRF2

Nuclear factor-like 2

OXPHOS

Oxidative phosphorylation

PGC-1

Peroxisome proliferator-activated receptor γ coactivator-1

PHD

Prolylhydroxylase

PI3K

Phosphoinositide 3-kinase

PKB/Akt

Protein kinase B

ROS

Reactive oxygen species

SDH

Succinate dehydrogenase

SOD

Superoxide dismutase

SRC2

Steroid receptor coactivator 2

SREBP

Sterol regulatory element-binding protein

STAT3

Signal transducer and activator of transcription 3

TCA (cycle)

Tricarboxylic acid (cycle)

TET (enzyme)

Ten-eleven translocation (enzyme)

Notes

Acknowledgments

Work at the authors’ lab is supported by a Starting Grant from the European Research Council (ERC No. 243188 TUMETABO), Interuniversity Attraction Pole (IAP) grant #UP7-03 from the Belgian Science Policy Office (Belspo), an Action de Recherche Concertée from the Communauté Française de Belgique (ARC 14/19-058), the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS), the Télévie, the Belgian Fondation contre le Cancer (2012-186), the Belgian Federal Agency for Nuclear Control (FANC-AFCN), the Louvain Foundation and the UCL Fonds Spéciaux de la Recherche (FSR). Pierre Sonveaux is a F.R.S.-FNRS Research Associate, Paolo E. Porporato a F.R.S.-FNRS Postdoctoral Fellow and Valéry L. Payen a F.R.S.-FNRS PhD Fellow. Bjorn Baselet is a grantee of the Belgian Nuclear Research Center (SCK·CEN).

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© Springer International Publishing 2015

Authors and Affiliations

  • Paolo E. Porporato
    • 1
  • Valéry L. Payen
    • 1
  • Bjorn Baselet
    • 1
    • 2
  • Pierre Sonveaux
    • 1
  1. 1.Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC)Université catholique de Louvain (UCL)BrusselsBelgium
  2. 2.Radiobiology Unit, Belgian Nuclear Research CentreSCK·CEN2400 MolBelgium

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