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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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.
Journal ArticleDOI
Emergence of neural encoding of auditory objects while listening to competing speakers
Nai Ding,Jonathan Z. Simon +1 more
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.
Journal ArticleDOI
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.
Journal ArticleDOI
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 activates acid sphingomyelinase via a redox mechanism and releases ceramide to trigger apoptosis.
C A Dumitru,Erich Gulbins +1 more
TL;DR: It is demonstrated that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and CD95 activate the ASM via a redox mechanism resulting in release of Ceramide and formation of ceramide-enriched membrane platforms that are required for the signaling of TRAIL-DR5 complexes under physiological conditions.
Journal ArticleDOI
Drug targeting of sphingolipid metabolism: sphingomyelinases and ceramidases.
TL;DR: The history, current uses and future directions for various small molecule inhibitors, and studies in which inhibitors of sphingolipid metabolizing enzymes have been used to effectively treat models of human disease are reviewed.
Journal ArticleDOI
Ceramide Recruits and Activates Protein Kinase C ζ (PKCζ) within Structured Membrane Microdomains
Todd E. Fox,Kristy L. Houck,Sean M. O’Neill,Murali Nagarajan,Thomas C. Stover,Pawel T. Pomianowski,Onur Unal,Jong K. Yun,Stanley J. Naides,Mark Kester +9 more
TL;DR: It is demonstrated that structured membrane microdomains are necessary for ceramide-induced activation of PKCζ and resultant diminished Akt activity, leading to vascular smooth muscle cell growth arrest.
Journal ArticleDOI
Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation
Margaret A. Park,Guo Zhang,Aditi Pandya Martin,Hossein A. Hamed,Clint Mitchell,Philip B. Hylemon,Martin R. Graf,Mohamed Rahmani,Kevin M. Ryan,Xiang Liu,Sarah Spiegel,James S. Norris,Paul B. Fisher,Steven Grant,Paul Dent +14 more
TL;DR: In this article, low doses of sorafenib and vorinostat interact in a synergistic fashion to kill carcinoma cells by activating CD95, and this drug combination is entering phase I trials.
Journal ArticleDOI
Ceramide 1-phosphate/ceramide, a switch between life and death.
TL;DR: An appropriate balance between the levels of these two metabolites seems to be crucial for cell and tissue homeostasis, and the activity of the enzymes that are involved in C1P and ceramide metabolism must be efficiently coordinated to ensure normal cell functioning.
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