Lactate and Lactate Transporters as Key Players in the Maintenance of the Warburg Effect

  • Andreia Pereira-Nunes
  • Julieta Afonso
  • Sara Granja
  • Fátima BaltazarEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1219)


Reprogramming of energy metabolism is a key hallmark of cancer. Most cancer cells display a glycolytic phenotype, with increased glucose consumption and glycolysis rates, and production of lactate as the end product, independently of oxygen concentrations. This phenomenon, known as “Warburg Effect”, provides several survival advantages to cancer cells and modulates the metabolism and function of neighbour cells in the tumour microenvironment. However, due to the presence of metabolic heterogeneity within a tumour, cancer cells can also display an oxidative phenotype, and corruptible cells from the microenvironment become glycolytic, cooperating with oxidative cancer cells to boost tumour growth. This phenomenon is known as “Reverse Warburg Effect”. In either way, lactate is a key mediator in the metabolic crosstalk between cancer cells and the microenvironment, and lactate transporters are expressed differentially by existing cell populations, to support this crosstalk.

In this review, we will focus on lactate and on lactate transporters in distinct cells of the tumour microenvironment, aiming at a better understanding of their role in the acquisition and maintenance of the direct/reverse “Warburg effect” phenotype, which modulate cancer progression.


Glycolysis Lactate Warburg effect Reverse Warburg effect Monocarboxylate transporters Lactate shuttles Cancer-associated fibroblasts Endothelial cells Immune cells 



This article has been developed under the scope of the project NORTE-01-0145-FEDER- 000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER), and through the Competitiveness Factors Operational Programme (COMPETE) and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. AP, JA and SG received fellowships from FCT, ref. SFRH/BD/148476/2019, SFRH/BPD/116784/2016 and SFRH/BPD/117858/2016, respectively.

Competing Interests

The authors declare no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Andreia Pereira-Nunes
    • 1
    • 2
  • Julieta Afonso
    • 1
    • 2
  • Sara Granja
    • 1
    • 2
  • Fátima Baltazar
    • 1
    • 2
    Email author
  1. 1.Life and Health Sciences Research Institute (ICVS), School of MedicineUniversity of MinhoBragaPortugal
  2. 2.ICVS/3B’s – PT Government Associate LaboratoryBraga/GuimarãesPortugal

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