Description
We first reported the recruitment of Fas/CD95 receptor in lipid rafts as a new way to regulate apoptosis in cancer cells, thus identifying lipid rafts as a novel therapeutic target. This finding opened a new therapeutic approach in cancer treatment, and we are devoted to uncover the role of lipid rafts in regulating cell death and survival. We have coined the term CASMER, as an acronym for “cluster of apoptotic signaling molecule-enriched rafts”, to refer to the recruitment of death receptors together with downstream apoptotic signaling molecules in aggregated rafts, thus leading to a raft-based supramolecular entity playing a major role in apoptosis regulation. We are mainly involved in the study of the mechanism of action of APLs as anticancer drugs against both hematological and solid tumors, especially the ether phospholipid edelfosine, which is considered as the first lipid raft-targeted drug. Furthermore, major interests in our lab also include the search for new drugs and therapeutic targets in pancreatic cancer, as well as the elucidation of the role of cancer stem cells in pancreatic cancer, and other additional gastrointestinal cancers, as a major target in cancer therapy. In addition, we are studying neutrophil development to understand how a proapoptotic phenotype is generated. We are also analyzing new pro-cell death routes in additional biological systems, including yeast and C. elegans, which in turn are being used as model organisms to uncover the mechanism of action of APLs. Overall, our major focus is the identification of novel targets, and the design of new therapeutic agents and approaches, to eventually induce the onset of cell death in tumor cells as an apoptosis- or cell death-targeted therapy in cancer. Particular emphasis is placed on the role of subcellular structures, including lipid raft membrane domains, endoplasmic reticulum and mitochondria, as major targets for cancer therapy and in the mechanism of action of APLs. In addition, we are analyzing how APLs can promote distinct types of cell death in different cancer cells, and trying to understand the triggers and signaling cross-talk controlling cell death commitment. As a result of the ability of edelfosine to promote cell death in different biological systems, we are also studying the underlying mechanisms involved in the antiparasitic action of this ether lipid.
Objectives
– Characterization and role of membrane rafts in apoptosis induction and cancer chemotherapy.
– Functional relationship between membrane rafts and subcellular structures affecting cell fate.
– Lipid metabolism in cancer cell development and therapy.
– Search for novel anticancer drugs targeting cell death in tumor cells.
– Mechanism of action of antitumor ether lipids (also known as alkylphospholipid analogs, APLs) as pro-cell death agents against cancer cells. Identification of distinct types of cell death induced by APLs.
- Analysis of cell death in cancer stem cells and cancer stem cell targeting in cancer therapy.
– Role and mechanisms of action of antitumor APLs as drugs for additional biomedical applications (inflammatory diseases, leishmaniasis, additional parasitic diseases).
– Inflammation and cancer relationship.
– Role of neutrophils and arginase in cancer.
– Neutrophils as a model system for the search of new therapeutic targets in cancer.
– Targeting of cancer stem cells.
– Use of additional biological systems (yeast, Caenorhabditis elegans) to uncover new signaling routes regulating cell death and to study the mechanisms of action of APLs and additional anticancer drugs.
Members