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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Local Circuits for Contrast Normalization and Adaptation Investigated with Two-Photon Imaging in Cat Primary Visual Cortex
TL;DR: It is found that a local patch of excitatory neurons has a large diversity of contrast tunings, which effectively extends the range of contrast that can be encoded instantaneously in cortex and provides new insights into the circuits and mechanisms underlying cortical adaptation and gain control.
Journal ArticleDOI
Manipulation of the Sphingolipid Rheostat Influences the Mediator of Flow-Induced Dilation in the Human Microvasculature.
TL;DR: Sphingolipid metabolites play a critical role in determining the mediator of FID in human resistance arterioles, and multiple targets exist within this biolipid pathway to treat microvascular dysfunction and potentially improve patient outcomes.
Journal ArticleDOI
Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in acute myelogenous leukemia—Impact on enzyme activity and response to cytotoxics
Samy A.F. Morad,Su Fern Tan,David J. Feith,Mark Kester,David F. Claxton,Thomas P. Loughran,Brian M. Barth,Todd E. Fox,Myles C. Cabot +8 more
TL;DR: These results show the versatility of adjuvant triphenylethylene with ceramide-centric therapies for magnifying therapeutic potential in AML, and could serve as effective strategies, even in the multidrug-resistant setting.
Journal ArticleDOI
Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis
Lufang Chen,Xiaodong Lu,Tiantian Zeng,Yuanyuan Chen,Qian Chen,Weijiang Wu,Xun Yan,Honghua Cai,Zhijian Zhang,Qixiang Shao,Wenxin Qin +10 more
TL;DR: The data demonstrates that lass2 is a protective gene against DEN-induced liver tumourigenesis; and upregulation of the TGF-β1-Smad4-PAI-1 axis may contribute to the vulnerability of Lass2-knockout mice to DEN.
Journal ArticleDOI
A role for ceramide glycosylation in resistance to oxaliplatin in colorectal cancer.
James P. Madigan,Robert W. Robey,Joanna E. Poprawski,Huakang Huang,Christopher J. Clarke,Michael M. Gottesman,Myles C. Cabot,Daniel W. Rosenberg +7 more
TL;DR: This study shows that GCS protein levels are greatly increased in human CRC specimens, compared to matched, normal colonic mucosa, and that high levels of UGCG gene expression are significantly associated with decreased disease-free survival in colorectal cancer patients.
References
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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.
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