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Journal ArticleDOI

Ceramide-orchestrated signalling in cancer cells

Samy A.F. Morad, +1 more
- 01 Jan 2013 - 
- Vol. 13, Iss: 1, pp 51-65
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.

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Citations
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Journal ArticleDOI

The equilibrium between long and very long chain ceramides is important for the fate of the cell and can be influenced by co-expression of CerS.

TL;DR: The data indicate that an increase in ceramide production per se is not critical for cell survival, but the equilibrium between long and very long chain ceramides and possibly protein/protein interactions determine the fate of the cell.
Journal ArticleDOI

Value-based attentional capture influences context-dependent decision-making

TL;DR: Behavioral and electrophysiological data suggest that value- based attentional capture and value-based normalization jointly mediate the influence of context on free-choice decision-making.
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Dopamine Regulates Two Classes of Primate Prefrontal Neurons That Represent Sensory Signals

TL;DR: It is found that DA modulation of prefrontal neurons is not uniform but tailored to specialized neuronal classes, and DA might play an important role in shaping how the PFC initiates appropriate behavior in response to changes in the sensory environment.
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Correlations in V1 Are Reduced by Stimulation Outside the Receptive Field

TL;DR: The results suggest that normalization signals may be an important mechanism for modulating correlations, and present annular stimuli that encircled—but did not impinge upon—the RFs of the recorded cells, which reduced correlations in the absence of stimulation of the RF.
Journal ArticleDOI

IGFBP-3: a cell fate pivot in cancer and disease.

TL;DR: The literature is reviewed on the paradoxical nature of IGFBP-3, its pro-apoptotic and growth-inhibitory actions versus its cytoprotective andgrowth-potentiating properties, and the implications of targeting IGF BP-3 for treatment of disease.
References
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Journal ArticleDOI

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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.
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Apoptosis: a link between cancer genetics and chemotherapy.

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FoxO3 controls autophagy in skeletal muscle in vivo.

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Targeting mitochondria for cancer therapy

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.

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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