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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

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TL;DR: The increased expression and altered trafficking of lysosomal enzymes participates in tissue invasion, angiogenesis and sensitization to the lyssomal death pathway, but l Lysosomal heat-shock protein 70 locally prevents lysOSomal-membrane permeabilization.
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Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy.

TL;DR: The role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl -2 family of proteins are reviewed.
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Ionizing radiation acts on cellular membranes to generate ceramide and initiate apoptosis.

TL;DR: The present studies show that ionizing radiation, like TNF, induces rapid sphingomyelin hydrolysis to ceramide and apoptosis in bovine aortic endothelial cells and suggest an alternative to the hypothesis that direct DNA damage mediates radiation-induced cell kill.
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Acid Sphingomyelinase–Deficient Human Lymphoblasts and Mice Are Defective in Radiation-Induced Apoptosis

TL;DR: It is shown that lymphoblasts from Niemann-Pick patients, which have an inherited deficiency of acid sphingomyelinase activity, fail to respond to ionizing radiation with ceramide generation and apoptosis.
Journal ArticleDOI

Sphingosine 1-phosphate and cancer.

TL;DR: There is substantial evidence that sphingosine 1-phosphate (S1P) is involved in cancer and the potential for new therapeutics designed to alter S1P signalling and function in cancer is examined.
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