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
A plausible neural circuit for decision making and its formation based on reinforcement learning
Hui Wei,Dawei Dai,Yijie Bu +2 more
TL;DR: A neural circuit to achieve the behavioral logic rules by strictly following the electrophysiological characteristics of biological neurons and anatomical facts is designed, which helps establish a transitional bridge between the microscopic activity of the nervous system and macroscopic animal behavior.
Journal ArticleDOI
3-Ketosphinganine provokes the accumulation of dihydroshingolipids and induces autophagy in cancer cells
Yadira F. Ordóñez,Jèssica González,Carmen Bedia,Josefina Casas,José Luis Abad,Antonio Delgado,Antonio Delgado,Gemma Fabriàs +7 more
TL;DR: It is shown that 3-ketosphinganine and its dideuterated analog at C4 (d2KSa) are metabolized to produce high levels of dihydrosphingolipids in HGC27, T98G and U87MG cancer cells and that cells respond to d2 KSa treatment with induction of autophagy.
Journal ArticleDOI
Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load
Lisa Holper,L D Van Brussel,Liane Schmidt,S Schulthess,Christopher J. Burke,Kenway Louie,Erich Seifritz,Philippe N. Tobler +7 more
TL;DR: It is suggested that mnemonic processes can constrain normalization of neural value representations, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk.
Journal ArticleDOI
The hyaluronic acid inhibitor 4-methylumbelliferone is an NSMase2 activator—role of Ceramide in MU anti-tumor activity
TL;DR: The mechanism of the MU anticancer initially involves NSMase2/ceramide/PP2A/AKT/HAS2/caspase-3/p53/SIRT1 and the calpain signaling pathway, suggesting that ceramides play a key role in the ability of a tumor to become aggressively metastatic and grow.
Posted ContentDOI
Subpopulations of neurons in lOFC encode previous and current rewards at time of choice
David L Hocker,Carlos D. Brody,Carlos D. Brody,Cristina Savin,Cristina Savin,Christine M Constantinople +5 more
TL;DR: The authors found five distinct clusters of lateral orbitofrontal cortex (lOFC) neurons, either based on clustering of their trial-averaged peristimulus time histograms (PSTHs), or a feature space defined by their average conditional firing rates aligned to different task variables.
References
More filters
Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
Apoptosis: a link between cancer genetics and chemotherapy.
TL;DR: Understanding the molecular events that contribute to drug-induced apoptosis, and how tumors evade apoptotic death, provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to anticancer drug design and therapy.
Journal ArticleDOI
FoxO3 controls autophagy in skeletal muscle in vivo.
Cristina Mammucari,Giulia Milan,Vanina Romanello,Eva Masiero,Ruediger Rudolf,Paola Del Piccolo,Steven J. Burden,Raffaella Di Lisi,Claudia Sandri,Jinghui Zhao,Alfred L. Goldberg,Stefano Schiaffino,Marco Sandri +12 more
TL;DR: FoxO3 controls the two major systems of protein breakdown in skeletal muscle, the ubiquitin-proteasomal and autophagic/lysosomal pathways, independently and is pointed to as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved.
Journal ArticleDOI
Targeting mitochondria for cancer therapy
Simone Fulda,Lorenzo Galluzzi,Lorenzo Galluzzi,Lorenzo Galluzzi,Guido Kroemer,Guido Kroemer,Guido Kroemer +6 more
TL;DR: The mitochondrial metabolism of cancer cells is deregulated owing to the use of glycolytic intermediates, which are normally destined for oxidative phosphorylation, in anabolic reactions and activation of the cell death machinery by stimulating mitochondrial membrane permeabilization could therefore be promising therapeutic approaches.
Journal ArticleDOI
Biologically active sphingolipids in cancer pathogenesis and treatment.
Besim Ogretmen,Yusuf A. Hannun +1 more
TL;DR: This work has shown that ceramide — a central molecule in sphingolipid metabolism — in effect functions as a tumour-suppressor lipid, inducing antiproliferative and apoptotic responses in various cancer cells, and that S1P induces responses that, on aggregate, render S 1P a tumours-promoting lipid.
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