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Sphingolipids in cancer

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Abstract

The bioactive sphingolipids including, ceramide, sphingosine, and sphingosine-1-phosphate (S1P) have important roles in several types of signaling and regulation of many cellular processes including cell proliferation, apoptosis, senescence, angiogenesis, and transformation. Recent accumulating evidence suggests that ceramide- and S1P-mediated pathways have been implicated in cancer development, progression, and chemotherapy. Ceramide mediates numerous cell-stress responses, such as induction of apoptosis and cell senescence, whereas S1P plays pivotal roles in cell survival, migration, and inflammation. These sphingolipids with opposing roles can be interconverted within cells, suggesting that the balance between them is related to cell fate. Importantly, these sphingolipids are metabolically related through actions of enzymes including ceramidases, ceramide synthases, sphingosine kinases, and S1P phosphatases thereby forming a network of metabolically interrelated bioactive lipid mediators whose importance in normal cellular function and diseases is gaining appreciation. In this review, we summarize involvement of sphingolipids and their related enzymes in pathogenesis and therapy of cancer and discuss future directions of sphingolipid field in cancer research.

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Acknowledgments

This work was supported by National Institutes of Health grants P01CA97132 and R01CA124687. We regret being unable to cite other important studies because of space limitations.

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The authors declare no conflict of interest.

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  1. University of Hawaii Cancer Center, 651 Ilalo Street, BSB #222H, Honolulu, HI, 96813, USA

    Hideki Furuya, Yoshiko Shimizu & Toshihiko Kawamori

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  1. Hideki Furuya
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  2. Yoshiko Shimizu
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  3. Toshihiko Kawamori
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Correspondence to Toshihiko Kawamori.

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Furuya, H., Shimizu, Y. & Kawamori, T. Sphingolipids in cancer. Cancer Metastasis Rev 30, 567–576 (2011). https://doi.org/10.1007/s10555-011-9304-1

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