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Bioactive Sphingolipids in Cancer Biology and Therapy pp 81–106Cite as

Sphingolipids as Mediators of Breast Cancer Progression, Metastasis, Response and Resistance to Chemotherapy

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Abstract

Approximately 250,000 people are diagnosed with breast cancer and 40,000 people die from the disease annually in the United States. Significant effort has been put into developing a thorough understanding of the molecular and genetic events that contribute to tumor progression due to mounting evidence that breast cancers are driven by predictable and identifiable genetic mutations, Sphingolipids modulate many of the growth, apoptosis, inflammatory, and angiogenic pathways that breast carcinomas rely on. Recent work in the field of sphingolipidomics has identified many key roles for the sphingolipids in breast tumor progression and identified signaling roles in each of the molecular subtypes of breast cancer. For example, in luminal type tumors, increased expression of ceramide producing enzymes and high levels of complex sphingolipids are associated with poor outcomes and multi-drug resistance. In basal type breast tumors CERT and GCS play a role in resistance to taxanes suggesting that targeting these pathways may be an effective route for the treatment of aggressive triple negative tumors. The role of sphingolipids in Her2-like tumors has not been thoroughly studied. However, CERK has been identified as potential driver of Her2-like tumors. Clearly, sphingolipid signaling in tumor modulation is both complex and vital. By integrating sphingolipid signaling into the molecular characterization of breast tumors, new opportunities for targeted intervention are identified. It is increasingly apparent that modulating sphingolipid levels in tumors will be an effective and powerful method for the treatment of breast cancer.

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Acknowledgements

The authors would like to acknowledge the SUNY Stony Brook Bioinformatics Facility. The results presented in Fig. 1 are based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. This work is partly supported by NCI grant P01 CA097132. We thank Dr. Christopher J. Clarke for careful review of this manuscript.

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Authors and Affiliations

  1. Department of Medicine, Stony Brook University, 178 Health Sciences Center, Stony Brook, NY, 11794, USA

    Benjamin Newcomb

  2. Stony Brook University Cancer Center, 178 Health Sciences Center, Stony Brook, NY, 11794, USA

    Benjamin Newcomb

  3. Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA

    Yusuf A. Hannun

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  1. Benjamin Newcomb
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Correspondence to Yusuf A. Hannun .

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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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Newcomb, B., Hannun, Y.A. (2015). Sphingolipids as Mediators of Breast Cancer Progression, Metastasis, Response and Resistance to Chemotherapy. 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_4

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