Glioblastoma Stem-Like Cells, Metabolic Strategy to Kill a Challenging Target

Over the years, substantial evidence has definitively confirmed the existence of cancer stem-like cells within tumors such as Glioblastoma (GBM). The importance of Glioblastoma stem-like cells (GSCs) in tumor progression and relapse clearly highlights that cancer eradication requires killing of GSCs that are intrinsically resistant to conventional therapies as well as eradication of the non-GSCs cells since GSCs emergence relies on a dynamic process. The past decade of research highlights that metabolism is a significant player in tumor progression and actually might orchestrate it. The growing interest in cancer metabolism reprogrammation can lead to innovative approaches exploiting metabolic vulnerabilities of cancer cells. These approaches are challenging since they require overcoming the compensatory and adaptive responses of GSCs. In this review, we will summarize the current knowledge on GSCs with a particular focus on their metabolic complexity. We will also discuss potential approaches targeting GSCs metabolism to potentially improve clinical care

Low-dose pesticide mixture induces senescence in normal mesenchymal stem cells (MSC) and promotes tumorigenic phenotype in premalignant MSC

Humans are chronically exposed to multiple environmental pollutants such as pesticides with no significant evidence about the safety of such poly-exposures. We exposed mesenchymal stem cells (MSC) to very low doses of mixture of seven pesticides frequently detected in food samples for 21 days in vitro. We observed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis but did not initiate a tumorigenic transformation. In modified MSC in which a premalignant phenotype wasinduced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro andin vivo after cell implantation, in all nude mice. Our results suggest that a commoncombination of pesticides can induce a premature ageing of adult MSC, and as such couldaccelerate age-related diseases. Exposure to pesticide mixture may also promote thetumorigenic transformation in a predisposed stromal environment

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes

Deficiency of the endoplasmic reticulum (ER) protein seipin results in generalized lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin-deficient patient cells. A subset of seipin is enriched at ER-mitochondria contact sites (MAMs) in human and mouse cells and localizes in the vicinity of calcium regulators SERCA2, IP3R, and VDAC. Seipin association with MAM calcium regulators is stimulated by fasting-like stimuli, while seipin association with lipid droplets is promoted by lipid loading. Acute seipin removal does not alter ER calcium stores but leads to defective mitochondrial calcium import accompanied by a widespread reduction in Krebs cycle metabolites and ATP levels. In mice, inducible seipin deletion leads to mitochondrial dysfunctions preceding the development of metabolic complications. Together, these data suggest that seipin controls mitochondrial energy metabolism by regulating mitochondrial calcium influx at MAMs. In seipin-deficient adipose tissue, reduced ATP production compromises adipocyte properties, contributing to lipodystrophy pathogenesis.Peer reviewe

Nourrir la planète : La proximité est-elle vecteur de solidarités ?

National audienc

Nourrir la planète : La proximité est-elle vecteur de solidarités ?

National audienc

UNE NOUVELLE PROTEINE DECOUPLANTE MITOCHONDRIALE UCP2 (LE GENE, LA PROTEINE ET SES ROLES PHYSIOLOGIQUES )

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Targeting CD8 T-Cell Metabolism in Transplantation

International audienceInfiltration of effector CD8 T cells plays a major role in allograft rejection, and increases in memory and terminally differentiated effector memory CD8 T cells are associated with long-term allograft dysfunction. Alternatively, CD8 regulatory T cells suppress the inflammatory responses of effector lymphocytes and induce allograft tolerance in animal models. Recently, there has been a renewed interest in the field of immunometabolics and its important role in CD8 function and differentiation. The purpose of this review is to highlight the key metabolic pathways involved in CD8 T cells and to discuss how manipulating these metabolic pathways could lead to new immunosuppressive strategies for the transplantation field