How ceramides affect the development of colon cancer: from normal colon to carcinoma

Nadine Merz, Jennifer Christina Hartel, Sabine Grösch
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Abstract

The integrity of the colon and the development of colon cancer depend on the sphingolipid balance in colon epithelial cells. In this review, we summarize the current knowledge on how ceramides and their complex derivatives influence normal colon development and colon cancer development. Ceramides, glucosylceramides and sphingomyelin are essential membrane components and, due to their biophysical properties, can influence the activation of membrane proteins, affecting protein–protein interactions and downstream signalling pathways. Here, we review the cellular mechanisms known to be affected by ceramides and their effects on colon development. We also describe which ceramides are deregulated during colorectal carcinogenesis, the molecular mechanisms involved in ceramide deregulation and how this affects carcinogenesis. Finally, we review new methods that are now state of the art for studying lipid-protein interactions in the physiological environment.

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结肠的完整性和结肠癌的发展取决于结肠上皮细胞中的鞘脂平衡。在这篇综述中,我们总结了目前关于神经酰胺及其复合衍生物如何影响正常结肠发育和结肠癌发展的知识。神经酰胺、葡萄糖基甘油酯和鞘磷脂是重要的膜成分,由于其生物物理特性,可影响膜蛋白的活化,从而影响蛋白质间的相互作用和下游信号通路。在此,我们回顾了已知受神经酰胺影响的细胞机制及其对结肠发育的影响。我们还描述了哪些神经酰胺在结直肠癌发生过程中会发生失调、神经酰胺失调所涉及的分子机制以及这种失调对癌变的影响。最后,我们回顾了目前最先进的研究生理环境中脂质与蛋白质相互作用的新方法。
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