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Glycolytic contribution to cancer growth and metastasis

Objective

Cancer lethality is most often associated to occurrence of distant metastases. To grow and become aggressive, cancers may undergo 2 critical adaptations: the glycolytic switch, corresponding to uncoupling glycolysis from the tricarboxylic acid (TCA) cycle, and the angiogenic switch, promoting neovascularization. In this high risk/high gain research program, we propose that the glycolytic switch precedes and promotes angiogenesis and metastatic dissemination in most types of cancer. We further envision that lactate, the end product of glycolysis, interfaces glycolysis and the latter processes through activation of hypoxia-inducible factor HIF-1. A thorough characterization of the molecular pathway(s) initiated by lactate (using transcriptomic, gene silencing, enzymatic and pharmacological interventions) has the potential to unravel new therapeutic targets that would simultaneously inhibit the consequences of the glycolytic switch on cancer aggressiveness. We anticipate the plasma membrane lactate transporters of the (sodium) monocarboxylate transporter (S)MCT family to be key determinants of autocrine and paracrine lactate signaling in cancer. Modulation of their activity or expression (notably by the generation of (S)MCT knock out mice) could thus profoundly affect tumor angiogenesis and metastasis. Since hypoxia is a hallmark of cancer and glycolysis its direct consequence in cancer cells surviving to hypoxia, the findings could have important consequences for the treatment of virtually all types of cancers. It could also impact our understanding of other pathologies, such as wound healing and heart infarction, in which the interplay between glycolysis, HIF-1 activation and angiogenesis could play a critical role.

Field of science

  • /medical and health sciences/clinical medicine/cancer

Call for proposal

ERC-2009-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITE CATHOLIQUE DE LOUVAIN
Address
Place De L Universite 1
1348 Louvain La Neuve
Belgium
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 493 320
Principal investigator
Pierre Sonveaux (Prof.)
Administrative Contact
Anne Bovy (Ms.)

Beneficiaries (1)

UNIVERSITE CATHOLIQUE DE LOUVAIN
Belgium
EU contribution
€ 1 493 320
Address
Place De L Universite 1
1348 Louvain La Neuve
Activity type
Higher or Secondary Education Establishments
Principal investigator
Pierre Sonveaux (Prof.)
Administrative Contact
Anne Bovy (Ms.)