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. Fields of science natural scienceschemical sciencesinorganic chemistryalkali metalsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology 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 EU contribution € 1 493 320,00 Address PLACE DE L UNIVERSITE 1 1348 Louvain La Neuve Belgium See on map Region Région wallonne Prov. Brabant Wallon Arr. Nivelles Activity type Higher or Secondary Education Establishments Principal investigator Pierre Sonveaux (Prof.) Administrative Contact Anne Bovy (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITE CATHOLIQUE DE LOUVAIN Belgium EU contribution € 1 493 320,00 Address PLACE DE L UNIVERSITE 1 1348 Louvain La Neuve See on map Region Région wallonne Prov. Brabant Wallon Arr. Nivelles Activity type Higher or Secondary Education Establishments Principal investigator Pierre Sonveaux (Prof.) Administrative Contact Anne Bovy (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
