ABSTRACT
Sphingolipids (SLs) are a class of essential, bioactive lipids. The SL family includes over 4000 distinct molecules, characterized by their sphingoid base (long-chain aliphatic amine) backbone. SLs are key components of cell membranes, yet their roles go well beyond structure. SLs are involved in many cellular processes including cell differentiation, apoptosis, growth arrest and senescence. As cancer cells routinely display increased growth properties and escape from cell death, it has been suggested that enzymes involved in SL synthesis or catabolism may be altered in cancer cells. In this review, we discuss the role of SL pathway enzymes in cancer, and in acquired resistance to therapy. The use of inhibitors and gene silencing approaches targeting these SL pathways is also explored. Finally, we elaborate on the role of SL pathway enzymes in the tumor microenvironment and their effect on immune cell function.
Subject(s)
Immunity , Neoplasms/immunology , Sphingolipids/metabolism , Animals , Apoptosis , Cell Cycle , Cell Differentiation , Drug Resistance, Neoplasm , Humans , Lipid Metabolism , Molecular Targeted Therapy , Signal TransductionABSTRACT
Today's increased life expectancy highlights both age-related changes in body composition and a higher prevalence of obesity. Sarcopenic obesity (SO) is assuming a prominent role in cardio-metabolic risk because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). This review evaluates the related studies that have been published over the past 10 years in order to give an updated overview of this new syndrome. There is no consensus on the definition of SO due to the wide heterogeneity of diagnostic criteria and choice of body composition components needed to assess this phenotype. There is a growing body of evidence that the ethio-pathogenesis of SO is complex and multi-factorial, as the consequences are a combination of the outcomes of both sarcopenia and obesity, where the effects are maximised. In order to manage SO, it is important to make lifestyle changes that incorporate weight loss, physical exercise and protein supplementation.
