Projects

Tumour acidosis is a direct consequence of the metabolism of cancer cells. Anaerobic glycolysis contributes to it as well as respiration via the hydration of CO2 (CO2 + H2O --> H2CO3 --> H+ + bicarbonate). We have shown that acidosis of the microenvironment in turn influences the metabolism of certain tumour areas which then "forget" glucose in favor of glutamine and fatty acids. This research theme continues today with the study of the mechanisms involved in this metabolic "shift", the exploration of the consequences in terms of invasiveness and resistance to treatment, and the validation of therapeutic strategies taking advantage of this dissection work.

• ^{Dierge E, Debock E, Guilbaud C, Corbet C, Mignolet E, Mignard L, Bastien E, Dessy C, Larondelle Y, Feron O. Peroxidation of n-3 and n-6 polyunsaturated fatty acids in the acidic tumor environment leads to ferroptosis-mediated anticancer effects. Cell Metab. 2021 Aug 3;33(8):1701-1715.e5.}
• ^{Corbet C, Bastien E, Santiago de Jesus JP, Dierge E, Martherus R, Vander Linden C, Doix B, Degavre C, Guilbaud C, Petit L, Michiels C, Dessy C, Larondelle Y, Feron O. TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nat Commun. 2020 Jan 23;11(1):454.}
• ^{Corbet C, Feron O. Tumor acidosis: from the passenger to the driver's seat. Nature Reviews Cancer. 2017}
• ^{Corbet C, Feron O. Cancer cell metabolism and mitochondria: nutrient plasticity for TCA cycle fueling. Biochim Biophys Acta. 2017}
• ^{Corbet C, Pinto A, Martherus R, Santiago de Jesus JP, Polet F, Feron O. Acidosis Drives the Reprogramming of Fatty Acid Metabolism in Cancer Cells through Changes in Mitochondrial and Histone Acetylation. Cell Metab. 2016 Aug 9;24(2):311-23.}
• ^{Corbet C, Draoui N, Polet F, Pinto A, Drozak X, Riant O, Feron O. The SIRT1/HIF2α axis drives reductive glutamine metabolism under chronic acidosis and alters tumor response to therapy. Cancer Res. 2014 Oct 1;74(19):5507-19.}

Tumor hypoxia results from the deficiency of oxygen supply and the oxidative metabolism needs of the cancer cells. The consequences for the tumor are manifold. For example, the reducing environment complicates the adequate "folding" of proteins and subjects the cells to permanent stress of the endoplasmic reticulum (ER stress) and the instability of oxygenation favors tumour aggressiveness and resistance to treatment. This research is currently being carried out using photodynamic therapy capable of accentuating ER stress and promoting immunogenic death, which supports anti-tumor vaccination protocols; the cancers targeted here are skin cancers and mesothelioma. Other lines of research are the exploitation of a transcriptomic signature associated with hypoxia fluctuations for prognostic and predictive purposes of the evolution of breast and colon cancers, as well as the development new therapeutic stratgies exploiting the concept of collateral lethality.

• _{Vander Linden C, Corbet C, Bastien E, Martherus R, Guilbaud C, Petit L, Wauthier L, Loriot A, De Smet C, Feron O. Therapy-induced DNA methylation inactivates MCT1 and renders tumor cells vulnerable to MCT4 inhibition. Cell Rep. 2021 Jun 1;35(9):109202.}
• _{Corbet C, Bastien E, Draoui N, Doix B, Mignion L, Jordan BF, Marchand A, Vanherck JC, Chaltin P, Schakman O, Becker HM, Riant O and Feron O. Interruption of lactate uptake by inhibiting mitochondrial pyruvate transport unravels tumor growth inhibitory and radiosensitizing effects. Nature Comm 2018.}
• _{Michiels C, Tellier C, Feron O. Cycling hypoxia: A key feature of the tumor microenvironment. Biochim Biophys Acta. 2016 Aug;1866(1):76-86.}
• _{Pinto A, Mace Y, Drouet F, Bony E, Boidot R, Draoui N, Lobysheva I, Corbet C, Polet F, Martherus R, Deraedt Q, Rodríguez J, Lamy C, Schicke O, Delvaux D, Louis C, Kiss R, Kriegsheim AV, Dessy C, Elias B, Quetin-Leclercq J, Riant O, Feron O. A new ER-specific photosensitizer unravels (1)O2-driven protein oxidation and inhibition of deubiquitinases as a generic mechanism for cancer PDT. Oncogene. 2016 Jul 28;35(30):3976-85.}
• _{Boidot R, Branders S, Helleputte T, Rubio LI, Dupont P, Feron O. A generic cycling hypoxia-derived prognostic gene signature: application to breast cancer profiling. Oncotarget. 2014 Aug 30;5(16):6947-63.}
• _{Boidot R, Végran F, Meulle A, Le Breton A, Dessy C, Sonveaux P, Lizard-Nacol S, Feron O. Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer Res. 2012 Feb 15;72(4):939-48.}
• _{Végran F, Boidot R, Michiels C, Sonveaux P, Feron O. Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-κB/IL-8 pathway that drives tumor angiogenesis. Cancer Res. 2011 Apr 1;71(7):2550-60.}

^{Tumor section with differential staining for hypoxia (green)
and blood vessels (red) including perfused ones (blue).}