Tumor suppressive functions of ceramide: evidence and mechanisms

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• 作者：Sehamuddin Galadari (1) (2)
  Anees Rahman (1)
  Siraj Pallichankandy (1)
  Faisal Thayyullathil (1)
  
  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
  2. Al Jalila Foundation Research Centre ; P.O. Box 300100 ; Dubai ; United Arab Emirates
  
• 关键词：Ceramide ; Apoptosis ; Autophagy ; Senescence ; Tumor suppression ; Molecular targets
• 刊名：Apoptosis
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：20
• 期：5
• 页码：689-711
• 全文大小：1,179 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Cell Biology
  Biochemistry
  Virology
  
• 出版者：Springer Netherlands
• ISSN：1573-675X

文摘

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.