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
More filters
Journal ArticleDOI
Circulating ceramides as biomarkers of cardiovascular disease: Evidence from phenotypic and genomic studies.
TL;DR: In this article, the authors discuss the importance of DNA variants in genes involved in ceramide biosynthesis as key influencers of heritable, circulating ceramide levels and discuss mechanistic insights deriving from recent genomic studies.
Journal ArticleDOI
Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma.
Ayse Batova,Diego Altomare,Kim E. Creek,Robert K. Naviaux,Lin Wang,Kefeng Li,Erica Green,Richard T. Williams,Jane C. Naviaux,Mitchell B. Diccianni,Alice L. Yu,Alice L. Yu +11 more
TL;DR: The findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc- RCC and possibly other lipid storing cancers.
Journal ArticleDOI
Symbol addition by monkeys provides evidence for normalized quantity coding
Margaret S. Livingstone,Warren W Pettine,Krishna Srihasam,Brandon Moore,Istvan A. Morocz,Daeyeol Lee +5 more
TL;DR: Rhesus monkeys trained to associate 26 distinct symbols with 0–25 drops of reward found that they could combine symbolically represented magnitudes, and they transferred this ability to a novel symbol set, indicating that they were performing a calculation, not just memorizing the value of each combination.
Book ChapterDOI
Mechanism-based inhibitors of glycosidases: design and applications.
TL;DR: In this article, the authors describe the various catalytic reaction mechanisms employed by inverting and retaining glycosidase targets to release a highly reactive species within the active site of the enzyme.
Journal ArticleDOI
Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide.
Minglin Lin,Minglin Lin,Weijia Liao,Mingjun Dong,Rongping Zhu,Juan Xiao,Tian Sun,Zhiyong Chen,Bin Wu,Junfei Jin +9 more
TL;DR: It is reported that NSMase1, which converts sphingomyelin (SM) to ceramide, was significantly downregulated in HCC tissues and suppressed HCC cell growth and induced apoptosis via reduction of the SM/Cer ratio.
References
More filters
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.
Related Papers (5)
Principles of bioactive lipid signalling: lessons from sphingolipids
Biologically active sphingolipids in cancer pathogenesis and treatment.
Besim Ogretmen,Yusuf A. Hannun +1 more