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Dysregulation of Sphingolipid Metabolism in Melanoma: Roles in Pigmentation, Cell Survival and Tumor Progression

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Bioactive Sphingolipids in Cancer Biology and Therapy

Abstract

Over the last decades, the incidence of cutaneous malignant melanoma rapidly increased in Caucasian populations. Moreover, melanoma is a leading cause of cancer death and consequently has become a significant public health problem worldwide in fair-skinned populations. The discovery of the prevalent mutation BRAFV600E, which drives melanoma cell growth, has made this oncogenic protein an ideal therapeutic target. However, the beneficial effects of BRAF-directed therapies are usually short-lived due to the appearance of resistance, which leads to disease progression. This emphasizes the need to develop new therapeutic approaches that could overcome tumor relapse. Alterations in sphingolipid metabolism are associated with melanoma progression and represent an exploitable target for the development of novel chemotherapeutics. The aim of this review is to concentrate on the critical metabolites and enzymes that contribute to this metabolic dysregulation in melanoma, to discuss the emerging roles of sphingolipids on melanogenesis, tumor microenvironment and melanoma progression, and to highlight relevant therapeutic approaches applicable for melanoma treatment.

Author contributed equally with all other contributors

An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-3-319-20750-6_21

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Acknowledgements

Financial support by INSERM, Paul Sabatier University, Ligue Nationale Contre le Cancer (Equipe Labellisée 2013), the Italian Association of Cancer Research (AIRC, IG11365) and the French and Lebanese ministries of foreign affairs (MAEDI) and Higher Education and Research (MENESR) (PHC CEDRE, 30750VL) is gratefully acknowledged. D.G. is a recipient of a fellowship from Ligue Nationale Contre le Cancer.

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    Authors and Affiliations

    1. Inserm UMR1037, Equipe Labellisée Ligue Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse, Oncopole de Toulouse, 2 Avenue Hubert Curien, CS 53717, 31037, Toulouse Cedex 1, France

      David Garandeau, Marguerite Mrad, Thierry Levade & Nathalie Andrieu-Abadie Ph.D.

    2. Université Toulouse III Paul-Sabatier, Toulouse, France

      David Garandeau, Marguerite Mrad, Thierry Levade & Nathalie Andrieu-Abadie Ph.D.

    3. Laboratoire de Biochimie Métabolique, CHU, Toulouse, France

      Thierry Levade

    4. Unit of Clinical Pharmacology, National Research Council Institute of Neuroscience, Department of Biomedical and Clinical Sciences, University Hospital L. Sacco, Università di Milano, Milan, Italy

      Cristiana Perrotta

    5. Faculty of Sciences II, Chemistry Department, Lebanese University, Beirut, Lebanon

      Mona Diab-Assaf

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    1. David Garandeau
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    Correspondence to Nathalie Andrieu-Abadie Ph.D. .

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    Editors and Affiliations

    1. Stony Brook University, Stony Brook Cancer Center, Stony Brook, New York, USA

      Yusuf A. Hannun

    2. Dept. of Physiology & Biophysics, Stony Brook University, Stony Brook, New York, USA

      Chiara Luberto

    3. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

      Cungui Mao

    4. Dept. of Medicine, Stony Brook University, Stony Brook, New York, USA

      Lina Marie Obeid

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    Garandeau, D., Mrad, M., Levade, T., Perrotta, C., Andrieu-Abadie, N., Diab-Assaf, M. (2015). Dysregulation of Sphingolipid Metabolism in Melanoma: Roles in Pigmentation, Cell Survival and Tumor Progression. In: Hannun, Y., Luberto, C., Mao, C., Obeid, L. (eds) Bioactive Sphingolipids in Cancer Biology and Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-20750-6_6

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