Journal ArticleDOI
Ceramide-orchestrated signalling in cancer cells
Samy A.F. Morad,Myles C. Cabot +1 more
TLDR
This Review focuses on ceramide signalling and the targeting of specific metabolic junctures to amplify the tumour suppressive activities of ceramide.Abstract:
One crucial barrier to progress in the treatment of cancer has been the inability to control the balance between cell proliferation and apoptosis: enter ceramide. Discoveries over the past 15 years have elevated this sphingolipid to the lofty position of a regulator of cell fate. Ceramide, it turns out, is a powerful tumour suppressor, potentiating signalling events that drive apoptosis, autophagic responses and cell cycle arrest. However, defects in ceramide generation and metabolism in cancer cells contribute to tumour cell survival and resistance to chemotherapy. This Review focuses on ceramide signalling and the targeting of specific metabolic junctures to amplify the tumour suppressive activities of ceramide. The potential of ceramide-based therapeutics in the treatment of cancer is also discussed.read more
Citations
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Application of stable isotopes to investigate the metabolism of fatty acids, glycerophospholipid and sphingolipid species.
Josef Ecker,Gerhard Liebisch +1 more
TL;DR: This review provides an overview of strategies to track fatty acid, glycerophospholipid, and sphingolipids metabolism and the selection of stable isotope-labeled precursors and their mass spectrometric analysis is discussed.
Journal ArticleDOI
The emerging role of FTY720 (Fingolimod) in cancer treatment.
TL;DR: While the clinical transition of FTY720 is currently limited by its immune suppression effects, studies aiming at FTY 720 delivery and release together with identifying its key synergetic combinations and relevant patient subsets may lead to its rapid introduction into the clinic.
Journal ArticleDOI
Phospholipids and cholesterol: Inducers of cancer multidrug resistance and therapeutic targets.
Joanna Kopecka,Patrick Trouillas,Ana Čipak Gašparović,Elena Gazzano,Yehuda G. Assaraf,Chiara Riganti +5 more
TL;DR: Beyond the induction of MDR, lipid metabolism offers a remarkable opportunity to reverse MDR by using lipid analogues and repurposing lipid-targeting drugs that reprogram the lipid composition of drug resistant cells, hence rendering them drug sensitive.
Journal ArticleDOI
Ceramide and the mitochondrial respiratory chain.
Aviram Kogot-Levin,Ann Saada +1 more
TL;DR: The physiological significance of synthetic short and naturally occurring long chain ceramides in modulating mitochondrial function with emphasis on the MRC will be discussed and the most relevant findings linking ceramide to mitochondria are summarized.
Journal ArticleDOI
New insights on glucosylated lipids: Metabolism and functions
TL;DR: The biological functions and metabolism of these three glucosylated lipids, ceramide, cholesterol, and phosphatidic acid, are discussed.
References
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Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
Apoptosis: a link between cancer genetics and chemotherapy.
TL;DR: Understanding the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to anticancer drug design and therapy.
Journal ArticleDOI
FoxO3 controls autophagy in skeletal muscle in vivo.
Cristina Mammucari,Giulia Milan,Vanina Romanello,Eva Masiero,Ruediger Rudolf,Paola Del Piccolo,Steven J. Burden,Raffaella Di Lisi,Claudia Sandri,Jinghui Zhao,Alfred L. Goldberg,Stefano Schiaffino,Marco Sandri +12 more
TL;DR: FoxO3 controls the two major systems of protein breakdown in skeletal muscle, the ubiquitin-proteasomal and autophagic/lysosomal pathways, independently and is pointed to as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved.
Journal ArticleDOI
Targeting mitochondria for cancer therapy
Simone Fulda,Lorenzo Galluzzi,Lorenzo Galluzzi,Lorenzo Galluzzi,Guido Kroemer,Guido Kroemer,Guido Kroemer +6 more
TL;DR: The mitochondrial metabolism of cancer cells is deregulated owing to the use of glycolytic intermediates, which are normally destined for oxidative phosphorylation, in anabolic reactions and activation of the cell death machinery by stimulating mitochondrial membrane permeabilization could therefore be promising therapeutic approaches.
Journal ArticleDOI
Biologically active sphingolipids in cancer pathogenesis and treatment.
Besim Ogretmen,Yusuf A. Hannun +1 more
TL;DR: This work has shown that ceramide — a central molecule in sphingolipid metabolism — in effect functions as a tumour-suppressor lipid, inducing antiproliferative and apoptotic responses in various cancer cells, and that S1P induces responses that, on aggregate, render S 1P a tumours-promoting lipid.
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