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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STAT3 mediates C6-ceramide-induced cell death in chronic lymphocytic leukemia
Ushma A. Doshi,Jeremy Joseph Porter Shaw,Todd E. Fox,David F. Claxton,Thomas P. Loughran,Mark Kester +5 more
TL;DR: These results are the first to demonstrate an effect of ceramide on BTK, a critical kinase mediating the B-cell receptor signaling in CLL cells and suggest a novel and synergistic combination of CNL and BTK inhibitors for CLL treatment.
Posted ContentDOI
Feedforward inhibition allows input summation to vary in recurrent cortical networks
TL;DR: Optogenetic manipulations in awake mice expose how a transformation in a cortical network depends on internal network activity, and that transformation depend critically on feedforward inhibition – the fact that inputs to the cortex often make strong connections on both excitatory and inhibitory neurons.
Posted ContentDOI
Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb
TL;DR: Collectively, the response properties of GCs point to their role in specific and local processing, rather than global operations such as response normalization proposed for other interneurons.
Journal ArticleDOI
Ceramide Metabolism Enzymes-Therapeutic Targets against Cancer.
Ana Gomez-Larrauri,Upasana Das Adhikari,Upasana Das Adhikari,Marta Aramburu-Nuñez,Antía Custodia,Alberto Ouro +5 more
TL;DR: In this paper, a review highlights the importance of bioactive sphingolipids and their regulatory enzymes as targets for therapeutic interventions with especial emphasis in carcinogenesis and cancer dissemination.
Journal ArticleDOI
The scope and limits of a mechanistic view of computational explanation
TL;DR: This paper identifies several challenges facing their mechanistic account and sketches an alternative way of thinking about the epistemic roles of computational approaches used in the study of brain and cognition.
References
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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
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Journal ArticleDOI
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Simone Fulda,Lorenzo Galluzzi,Lorenzo Galluzzi,Lorenzo Galluzzi,Guido Kroemer,Guido Kroemer,Guido Kroemer +6 more
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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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