LIPOMET SIGNED

Project "LIPOMET" data sheet

The following table provides information about the project.

 Partnership

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 Project objective

We have recently identified metastasis-initiating cells (MICs) in several types of tumors (Nature, 2017)1. Intriguingly, MICs: (i) are exclusive in their ability to generate metastases when transplanted; (ii) express the fatty acid channel CD36 and have a unique lipid metabolic signature; (iii) are exquisitely sensitive to the levels of fat in circulation, thus providing a link between the predisposition of metastasis and dietary fat; (iv) are highly sensitive to CD36 inhibition, which almost completely abolishes their metastatic potential.

We still do not know how MICs promote metastasis or how MICs are influenced by dietary fat. In particular: (A) where are MICs located within the tumor, and does this location influence their behavior? How and where do they attach and expand at metastatic sites? (B) Why are MICs so sensitive to specific dietary lipids, and how do these lipids promote metastasis at the molecular and cellular levels? (C) Is the prolonged consumption of a high-fat diet a risk factor for developing metastatic tumors? If so, what are the underlying genetic and epigenetic causes for this effect? Can we revert these causes? To answer these questions, we will combine state-of-the-art in vivo functional models of metastasis, with quantitative metabolomics and proteomics, epigenetic and geographical position (3D) single-cell transcriptomic studies, as well as integrative computational analyses, using preclinical models and patientderived carcinomas of melanoma, oral cancer and breast cancer.

We expect our project to provide fundamental insights into the mechanisms of metastasis, and how they are influenced by diet. This is highly relevant as 1) large quantities of fatty acids are typically consumed in Western diets; and 2) metastasis is the leading cause of cancer-related deaths. We also tackle a timely medical unmet need by exploring the therapeutic anti-metastatic potential of targeting fatty acid metabolism in cancer patients.

 Publications