Targeting Lipid Rafts as a Strategy against Infection and Cancer

Lipid rafts are dynamic cholesterol- and sphingolipids-enriched membrane micro-domains that are present in all eukaryotic cells as well as in bacteria. Their importance for living cells is underlined by their involvement in several processes including bacterial and viral entry, or cancer. Pathogens and their components (including pore forming toxins) interact with lipid rafts to promote internalization or communication with the host cell through different and specific signalling molecules that dissociate and associate rapidly at these sites. Lipid rafts play an essential role in cancer adhesion and migration and they are or become particularly enriched of receptors involved in the regulation of intracellular signalling leading to death or survival cell programs activation underlying cancer growth as well as cancer control. In addition, the existence of raft-like microdomain as components of internal organelles membranes, including mitochondria, endoplasmic reticulum and nucleus contributes to clarify the importance of some sphingolipid/protein associations in the physiological and pathological processes responsible for determining cell fate. Therefore, targeting lipid rafts is emerging as an innovative strategy to limit intracellular pathogens in host cells and to increase the sensitivity to apoptosis/autophagy of different types of tumors. Since membrane fluidity plays a major role in drug transport and endocytic function, treatment of resistant cells with cholesterol and/or glycosphingolipids-targeting agents could also enhance anticancer drug transport to overcome acquired drug resistance. Novel mass spectroscopy methods and advanced microscopy will allow a better investigation of signalling complexes under normal conditions and after cholesterol depletion. The in-depth investigation of lipid membrane regulation is an essential step for a better understanding of the molecular and cellular basis of lipid-associated disorders.

The aim of this Research Topic is to gather recent and novel findings that elucidate how modifications of lipid rafts in terms of their composition and organization can limit pathogens' infection, as well as, contribute to an enhanced chemosensitivity of tumor cells. Areas to be covered in this Research Topic may include, but are not limited to:

• Lipid rafts/cholesterol and trafficking
• Chemical compounds influencing cholesterol/glycosphingolipids concentration, trafficking and organization
• Lipid rafts and viral entry
• Lipid rafts and intracellular bacteria
• Importance of cholesterol and lipid rafts for toxins-induced pore formation
• Phosphoinositides and pathogens
• Role of cholesterol and lipid rafts in cancer signalling
• Role of lipid rafts components in apoptosis/autophagy regulation during pathogens' infection
• Modification of membrane microdomains to enhance anti-cancer therapy