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Tumor suppressive functions of ceramide: evidence and mechanisms

  • THE ROLE OF SPHINGOLIPIDS AND LIPID RAFTS IN DETERMINING CELL FATE
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Abstract

Studies over the past two decades have identified ceramide as a multifunctional central molecule in the sphingolipid biosynthetic pathway. Given its diverse tumor suppressive activities, molecular understanding of ceramide action will produce fundamental insights into processes that limit tumorigenesis and may identify key molecular targets for therapeutic intervention. Ceramide can be activated by a diverse array of stresses such as heat shock, genotoxic damage, oxidative stress and anticancer drugs. Ceramide triggers a variety of tumor suppressive and anti-proliferative cellular programs such as apoptosis, autophagy, senescence, and necroptosis by activating or repressing key effector molecules. Defects in ceramide generation and metabolism in cancer contribute to tumor cell survival and resistance to chemotherapy. The potent and versatile anticancer activity profile of ceramide has motivated drug development efforts to (re-)activate ceramide in established tumors. This review focuses on our current understanding of the tumor suppressive functions of ceramide and highlights the potential downstream targets of ceramide which are involved in its tumor suppressive action.

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Acknowledgments

This work was financially supported by grants from the UAE University-National Research Foundation (31M097), Terry Fox Foundation for Cancer Research (21M093), The Sheikh Hamdan Award for Medical Sciences (MRG-60/2011-2012). SG is supported by the Al Jalila Foundation for Medical Education and Research.

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Authors and Affiliations

  1. Cell Signaling Laboratory, Department of Biochemistry, College of Medicine and Health Sciences, UAE University, Al Ain, PO Box 17666, Abu Dhabi, United Arab Emirates

    Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy & Faisal Thayyullathil

  2. Al Jalila Foundation Research Centre, P.O. Box 300100, Dubai, United Arab Emirates

    Sehamuddin Galadari

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  1. Sehamuddin Galadari
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  2. Anees Rahman
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Correspondence to Sehamuddin Galadari.

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Galadari, S., Rahman, A., Pallichankandy, S. et al. Tumor suppressive functions of ceramide: evidence and mechanisms. Apoptosis 20, 689–711 (2015). https://doi.org/10.1007/s10495-015-1109-1

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