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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

Sphingolipids and their metabolism in physiology and disease.

TL;DR: These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingoipid metabolism to key human diseases.
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Emergence of neural encoding of auditory objects while listening to competing speakers

TL;DR: Recording from subjects selectively listening to one of two competing speakers using magnetoencephalography indicates that concurrent auditory objects, even if spectrotemporally overlapping and not resolvable at the auditory periphery, are neurally encoded individually in auditory cortex and emerge as fundamental representational units for top-down attentional modulation and bottom-up neural adaptation.
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mTOR signalling and cellular metabolism are mutual determinants in cancer.

TL;DR: The interdependencies of mTOR signalling and metabolism pathways in cancer and how metabolic reprogramming in response to changes in m TOR signalling and vice versa can sustain tumorigenicity are discussed.
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Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development

TL;DR: The role of aberrant lipid biosynthesis in cancer cell migration and invasion, and in the induction of tumour angiogenesis, is explored.
Journal ArticleDOI

Early olfactory processing in Drosophila: mechanisms and principles.

TL;DR: This review summarizes the neurophysiology of the first two layers of this system: the peripheral olfactory receptor neurons and their postsynaptic targets in the antennal lobe and suggests some general principles with broad relevance to early sensory processing in other modalities.
References
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Journal ArticleDOI

TRAIL receptor-targeted therapeutics: resistance mechanisms and strategies to avoid them.

TL;DR: This review discusses recent findings about some of the ways these resistance mechanisms arise, potential biomarkers to identify TRAIL resistance in patients, and potential ways to circumvent resistance and resensitize tumors.
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Involvement of Dihydroceramide Desaturase in Cell Cycle Progression in Human Neuroblastoma Cells

TL;DR: The role of dihydroceramide desaturase as a key enzyme in the de novo pathway of ceramide generation was investigated in human neuroblastoma cells and treatment of SMS-KCNR cells with fenretinide inhibited Desaturase activity in a dose-dependent manner, suggesting a novel biological function for diHydroceramides.
Journal ArticleDOI

Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation

TL;DR: It is concluded that capsaicin induces apoptosis in PC-3 cells via ROS generation, JNK activation, ceramide accumulation, and second, ERK activation, and JNK as an upstream regulator of ceramide production.
Journal ArticleDOI

Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane.

TL;DR: It is demonstrated that Bax and ceramide induce MOMP synergistically, and previous findings that anti-apoptotic proteins disassemble ceramide channels suggest that ceramicamide channels, regulated by Bcl-2-family proteins, may be responsible for the MOMp during apoptosis.
Journal ArticleDOI

Remodeling of cellular cytoskeleton by the acid sphingomyelinase/ceramide pathway

TL;DR: It is found that cisplatin induces a transient elevation in ASMase activity and its redistribution to the plasma membrane and this translocation is blocked upon overexpression of a dominant-negative AsMaseS508A mutant and by a DN PKCδ.
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