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.
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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
Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and/or mitochondria?
TL;DR: It is shown that purified mitochondria as well as MAM are indeed able to generate ceramide in vitro through both ceramide synthase or reverse ceramidase, whereas the latter enzyme activity is barely detectable in microsomes.
Journal ArticleDOI
Protein phosphatase 2A negatively regulates insulin's metabolic signaling pathway by inhibiting Akt (protein kinase B) activity in 3T3-L1 adipocytes.
Satoshi Ugi,Takeshi Imamura,Hiroshi Maegawa,Katsuya Egawa,Takeshi Yoshizaki,Kun Shi,Toshiyuki Obata,Yousuke Ebina,Atsunori Kashiwagi,Jerrold M. Olefsky +9 more
TL;DR: PP2A is a negative regulator of insulin's metabolic signaling pathway by promoting dephosphorylation and inactivation of Akt and PKC λ and that most of the effects of PP2A to inhibit glucose transport are mediated through Akt.
Journal ArticleDOI
Ceramide Directly Activates Protein Kinase C ζ to Regulate a Stress-activated Protein Kinase Signaling Complex
TL;DR: It is demonstrated that ceramide induces cell cycle arrest by enhancing the ability of PKCζ to form a signaling complex with MEKK1, SEK, and SAPK.
Journal ArticleDOI
Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations.
TL;DR: The concentration of ceramide at which significant channel formation occurs is consistent with the level of mitochondrial ceramide that occurs during the induction phase of apoptosis (4 pmol ceramide/nanomole phospholipid).
Journal ArticleDOI
Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation.
Masataka Kohno,Michiko Momoi,Myat Lin Oo,Jihye Paik,Yong-Moon Lee,Krishnan Venkataraman,Youxi Ai,Ari Ristimäki,Henrik Fyrst,Hajime Sano,Daniel W. Rosenberg,Julie D. Saba,Richard L. Proia,Timothy Hla +13 more
TL;DR: It is shown that Sphk 1 is expressed and is required for small intestinal tumor cell proliferation in ApcMin/+ mice and that inhibitors of Sphk1 may be useful in the control of intestinal cancer.
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