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Role of Sphingolipids in Liver Cancer

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Bioactive Sphingolipids in Cancer Biology and Therapy

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Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and one of the leading causes of cancer-related deaths in the world. Unfortunately, current therapy is inefficient and advanced HCC is highly resistant to chemotherapy, making early diagnosis crucial for survival. HCC develops in the course of chronic liver disease and inflammation. Progressive non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and HCC and NAFLD incidence is expected to grow due to its association with obesity and type 2 diabetes. Sphingolipids (SLs) biology has evolved from the inceptive view of being considered mere structural components of membrane bilayers to the current status of critical second messengers involved in the regulation of myriads cell functions, including cell death pathways. A crucial mechanism underlying the therapeutic potential of cancer treatment involves ceramide species, which stand as the basis for the mode of action of chemotherapy and radiotherapy. However, many solid tumors, including HCC, develop strategies that counter this increase in ceramides, which blunt therapy efficacy and promotes treatment resistance. Understanding these pathways may provide novel strategies to exploit the potential of ceramide and SLs to multiply the therapeutic effect of chemotherapy in the treatment of liver cancer. The present chapter summarizes these pathways and highlights the potential of combinational therapy based on maneuvers to increase SLs to combat liver cancer.

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Acknowledgments

The work was supported by grants SAF-2011-23031, SAF-2012-34831 from Plan Nacional de I+D, Spain, the center grant P50-AA-11999 Research Center for Liver and Pancreatic Diseases funded by NIAAA/NIH, a grant from Fundació Marató de TV3, La Mutua Madrileña, PI11/0325 (META) grant from the Instituto Salud Carlos III, and by the support of CIBERehd.

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Authors and Affiliations

  1. Department of Cell Death and Proliferation, Instituto Investigaciones Biomédicas de Barcelona, CSIC, Barcelona, Spain

    Carmen Garcia-Ruiz, Albert Morales & José C. Fernández-Checa

  2. Liver Unit-Hospital Clinic-IDIBAPS and Centro de Investigación Biomédica en Red (CIBERehd), Barcelona, Spain

    Carmen Garcia-Ruiz, Albert Morales & José C. Fernández-Checa

  3. University of Southern California Research Center for Liver Diseases, Keck School of Medicine, USC, Los Angeles, CA, USA

    José C. Fernández-Checa

Authors
  1. Carmen Garcia-Ruiz
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  2. Albert Morales
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  3. José C. Fernández-Checa
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Correspondence to José C. Fernández-Checa .

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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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Garcia-Ruiz, C., Morales, A., Fernández-Checa, J.C. (2015). Role of Sphingolipids in Liver Cancer. 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_9

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