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:Â
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
Molecular mechanisms of ceramide-mediated CD95 clustering.
TL;DR: It is shown that ceramide in sphingolipid-rich membrane rafts mediates clustering of CD95, which is required for initiation of apoptosis, at least in some cell types.
Journal ArticleDOI
Systemic Delivery of Liposomal Short-Chain Ceramide Limits Solid Tumor Growth in Murine Models of Breast Adenocarcinoma
TL;DR: It is reported that the systemic i.v. delivery of C6-ceramide (C6) in a pegylated liposomal formulation significantly limited the growth of solid tumors in a syngeneic BALB/c mouse tumor model of breast adenocarcinoma.
Journal ArticleDOI
Calpain is required for macroautophagy in mammalian cells
Francesca Demarchi,Cosetta Bertoli,Tamara Copetti,Isei Tanida,Claudio Brancolini,Eeva-Liisa Eskelinen,Claudio Schneider +6 more
TL;DR: In calpain-deficient cells, autophagy is impaired with a resulting dramatic increase in apoptotic cell death, and immunostaining of the endogenous autophagosome marker LC3 and electron microscopy experiments demonstrate that autophagic is impaired in CAPNS1-deficiency cells.
Journal ArticleDOI
Ceramide induces p38 MAPK and JNK activation through a mechanism involving a thioredoxin-interacting protein-mediated pathway.
TL;DR: Ceramide exhibits a mechanism of transcriptional regulation involving up-regulation of Txnip expression, also induced by etoposide, which results in ASK1 activation, ER stress, and p38 and JNK phosphorylation, all leading to apoptosis.
Journal ArticleDOI
Ceramide starves cells to death by downregulating nutrient transporter proteins.
Garret Guenther,Eigen R. Peralta,Kimberly Romero Rosales,Susan Y. Wong,Leah J. Siskind,Aimee L. Edinger +5 more
TL;DR: The results support a model where ceramide kills cells by inducing intracellular nutrient limitation subsequent to nutrient transporter downregulation, and suggest that the cellular metabolic state is an important arbiter of the cellular response to ceramide.
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