Our research project at a glance
Abnormal lipid profiles are often associated with an altered metabolic phenotype in tumor cells, which has been recognized as a hallmark of cancer. Our aim is to elucidate how sphingolipid (SL) metabolism affects key biological processes underlying cancer development including cell death, proliferation, migration, tumor stroma remodeling as well as immune response. In particular, the contribution of SLs to skin melanoma and breast cancer is examined. Not only these forms of cancer are frequent and/or resistant to current therapies, but also they exhibit altered SL metabolism. Our ultimate goal is to target SL metabolism in order to improve therapeutic approach, i.e., to prevent tumor progression and overcome resistance to anticancer drugs, cytokines and immune cells.
Two main questions are addressed:
1/ How SL metabolism controls melanoma cells and their microenvironment?
The purpose of our project is triple:
- the identification and role of variants in genes encoding enzymes of SL metabolism in familial melanoma,
- the delineation of the effects of the oncometabolite sphingosine 1-phosphate (S1P) and its receptors on the communication between melanoma cells and their cellular microenvironment during initial progression,
- the understanding of the molecular mechanisms underlying the role of SL metabolism in the resistance of melanoma cells to current therapies.
2/ How SL metabolism affects the anticancer immune response?
We postulate that SL metabolism alterations in cancer cells modulate immune response, facilitating tumor escape from the immune system. We will investigate :
- the levels of SL metabolites in plasma and tumors according to the tumor infiltration by leukocytes,
- the causal role of SL metabolism alterations in the immunogenicity of cancer cells and their responses to immune and death effector molecules,
- the role of tumor SLs on tumor-infiltrating leukocytes in mouse models.
- Sphingosine 1-phosphate
- Tumor microenvironment
- Tumor necrosis factor
Labels and networks
Grants and funders
- Ligue Nationale Contre le Cancer
- Fondation pour la Recherche Médicale
- Union européenne
- Fondation ARC pour la Recherche sur le Cancer
- Université Toulouse 3 Paul Sabatier
- Campus France
- Région Occitanie Pyrénées – Méditerranée
- Institut National du Cancer
- Cancéropôle Grand Sud-Ouest
- Shire France
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