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A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
Published on: January 22, 2021
Sphingolipids in colon cancer
Mónica García-Barros1, Nicolas Coant1, Jean-Philip Truman1
1Department of Medicine and the Stony Brook Cancer Center, Health Science Center, Stony Brook University, 101 Nicolls Road, T15, 023, 11794, Stony Brook, NY, USA.
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.
Insights
Sphingolipids, crucial bioactive lipids, are increasingly implicated in colon cancer development and progression. Understanding their role, alongside the WNT/β-catenin pathway, offers new therapeutic avenues for this deadly disease.
Area of Science:
- Molecular Biology
- Oncology
- Lipid Metabolism
Background:
- Colorectal cancer remains a leading cause of mortality globally.
- Current therapeutic strategies for colon cancer show limited success despite advances in understanding molecular pathways.
- Sphingolipids, including ceramide, sphingosine, and sphingosine-1-phosphate, are vital bioactive lipids regulating cellular functions.
Purpose of the Study:
- To review the emerging roles of endogenous and dietary sphingolipids in colon cancer.
- To explore the intricate interactions between sphingolipids and the WNT/β-catenin signaling pathway.
- To highlight potential therapeutic targets within sphingolipid metabolism for colon cancer treatment.
Main Methods:
- Literature review of studies on sphingolipids and colon cancer.
- Analysis of research on sphingolipid metabolism and its enzymes in cancer.
- Examination of the cross-talk between sphingolipids and WNT/β-catenin signaling.
Main Results:
- Alterations in sphingolipid levels and metabolizing enzymes are frequently observed in various cancers, including colon cancer.
- Sphingolipids play multifaceted roles in colon cancer, influencing cell proliferation, survival, and migration.
- The WNT/β-catenin pathway is significantly modulated by sphingolipid metabolism, impacting intestinal homeostasis and cancer development.
Conclusions:
- Sphingolipids represent promising targets for novel colon cancer therapies.
- Targeting sphingolipid metabolism, particularly in conjunction with the WNT/β-catenin pathway, may offer improved treatment outcomes.
- Further research into dietary sphingolipids could reveal preventative or therapeutic strategies for colon cancer.
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