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
More filters
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
More filters
Journal ArticleDOI
A Phase I Clinical Trial of Safingol in Combination with Cisplatin in Advanced Solid Tumors
Mark A. Dickson,Richard D. Carvajal,Alfred H Merrill,Mithat Gonen,Lauren M. Cane,Gary K. Schwartz +5 more
TL;DR: Reversible dose-dependent hepatic toxicity was seen, as expected from preclinical data, and safingol, the first putative SphK inhibitor to enter clinical trials, can be safely administered in combination with cisplatin.
Journal ArticleDOI
Role of membrane sphingomyelin and ceramide in platform formation for Fas-mediated apoptosis
Michihiko Miyaji,Michihiko Miyaji,Zhe-Xiong Jin,Zhe-Xiong Jin,Shohei Yamaoka,Ryuichi Amakawa,Shirou Fukuhara,Satoshi B. Sato,Toshihide Kobayashi,Naochika Domae,Tsuneyo Mimori,Eda T. Bloom,Toshiro Okazaki,Hisanori Umehara,Hisanori Umehara +14 more
TL;DR: In this paper, the authors show that expression of membrane sphingomyelin (SM) enhances Fas-mediated apoptosis through increasing DISC formation, activation of caspases, efficient translocation of Fas into lipid rafts, and subsequent Fas clustering.
Journal ArticleDOI
Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase 3 in colon cancer cells
Shai White-Gilbertson,Thomas D. Mullen,Can E. Senkal,Ping Lu,Besim Ogretmen,Lina M. Obeid,Lina M. Obeid,Christina Voelkel-Johnson +7 more
TL;DR: Modulation of CerS6 expression may constitute a new therapeutic strategy to alter apoptotic susceptibility and is suggested to reverse TRAIL resistance in SW620 cells.
Journal ArticleDOI
GSK-3β acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 in ceramide-induced mitochondrial apoptosis
TL;DR: A role for GSK-3β is indicated in ceramide-induced apoptosis, in which GSK -3β acts downstream of PP2A and the PI 3-kinase-Akt pathway, and upstream of caspase-2 and caspases-8.
Journal ArticleDOI
Combining nanoliposomal ceramide with sorafenib synergistically inhibits melanoma and breast cancer cell survival to decrease tumor development.
TL;DR: A foundation is established for clinical trials evaluating the efficacy of combining sorafenib with nanoliposomal ceramide for treatment of cancers as well as for mechanistic basis for inhibition.
Related Papers (5)
Principles of bioactive lipid signalling: lessons from sphingolipids
Biologically active sphingolipids in cancer pathogenesis and treatment.
Besim Ogretmen,Yusuf A. Hannun +1 more