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Review
. 2014 May;1841(5):773-82.
doi: 10.1016/j.bbalip.2013.09.007. Epub 2013 Sep 21.

Sphingolipids in Colon Cancer

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Free PMC article
Review

Sphingolipids in Colon Cancer

Mónica García-Barros et al. Biochim Biophys Acta. .
Free PMC article

Abstract

Colorectal cancer is one of the major causes of death in the western world. Despite increasing knowledge of the molecular signaling pathways implicated in colon cancer, therapeutic outcomes are still only moderately successful. Sphingolipids, a family of N-acyl linked lipids, have not only structural functions but are also implicated in important biological functions. Ceramide, sphingosine and sphingosine-1-phosphate are the most important bioactive lipids, and they regulate several key cellular functions. Accumulating evidence suggests that many cancers present alterations in sphingolipids and their metabolizing enzymes. The aim of this review is to discuss the emerging roles of sphingolipids, both endogenous and dietary, in colon cancer and the interaction of sphingolipids with WNT/β-catenin pathway, one of the most important signaling cascades that regulate development and homeostasis in intestine. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

Keywords: Ceramide; Colorectal cancer; Dietary; Sphingolipids; Sphingosine; Sphingosine-1-phosphate.

Figures

Figure 1
Figure 1
Summary of the changes in sphingolipid metabolic enzyme described in colon cancer, along with an overview of the major roles in cell homeostasis. Figure based on figure 9 in Kono et. al. [65], with permission. SM: Sphingomyelin; alk-SMase: alkaline-Sphingomyelinase; nCDase: neutral Ceramidase; SPL: Sphingosine-1-P Lyase; S1P: Sphingosine-1-Phosphate; SPPase: Sphingosine-1-P Phosphatase; SK: Sphingosine Kinase; CerS: Ceramide Synthase and GCS: Glucosylceramide Synthase.
Figure 2
Figure 2
Summary of the effects of sphingolipids in colon cancer cells. LCL-30: ω-pyridinium bromide D-erythro-C16-ceramide; SM: Sphingomyelin; SPH: Sphingosine; DMS: N,N-dimethylsphingosine; CDase: Ceramidase; aSMase: acid Sphingomyelinase; TNF-α: Tumor Necrosis Factor alfa; CerS: Ceramide Synthase; TRAIL: TNF-Related Apoptosis-Inducing Ligand; S1P: Sphingosine 1 Phosphate; SK: Sphingosine Kinase.

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