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S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy

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Abstract

Sphingosine-1-phosphate (S1P) can regulate several physiological and pathological processes. S1P signaling via its cell surface receptor S1PR1 has been shown to enhance tumorigenesis and stimulate growth, expansion, angiogenesis, metastasis, and survival of cancer cells. S1PR1-mediated tumorigenesis is supported and amplified by activation of downstream effectors including STAT3, interleukin-6, and NF-κB networks. S1PR1 signaling can also trigger various other signaling pathways involved in carcinogenesis including activation of PI3K/AKT, MAPK/ERK1/2, Rac, and PKC/Ca, as well as suppression of cyclic adenosine monophosphate (cAMP). It also induces immunological tolerance in the tumor microenvironment, while the immunosuppressive function of S1PR1 can also lead to the generation of pre-metastatic niches. Some tumor cells upregulate S1PR1 signaling pathways, which leads to drug resistant cancer cells, mainly through activation of STAT3. This signaling pathway is also implicated in some inflammatory conditions leading to the instigation of inflammation-driven cancers. Furthermore, it can also increase survival via induction of anti-apoptotic pathways, for instance, in breast cancer cells. Therefore, S1PR1 and its signaling pathways can be considered as potential anti-tumor therapeutic targets, alone or in combination therapies. Given the oncogenic nature of S1PR1 and its distribution in a variety of cancer cell types along with its targeting advantages over other molecules of this family, S1PR1 should be considered a favorable target in therapeutic approaches to cancer. This review describes the role of S1PR1 in cancer development and progression, specifically addressing breast cancer, glioma, and hematopoietic malignancies. We also discuss the potential use of S1P signaling modulators as therapeutic targets in cancer therapy.

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Authors and Affiliations

  1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Narges Rostami, Afshin Nikkhoo, Bahman Yousefi & Mehdi Yousefi

  2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Narges Rostami

  3. Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

    Amir Ajjoolabady

  4. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Gholamreza Azizi

  5. Bioclinicum, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden

    Mohammad Hojjat-Farsangi

  6. The Persian Gulf Marine Biotechnology Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran

    Mohammad Hojjat-Farsangi

  7. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

    Ghasem Ghalamfarsa

  8. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Farhad Jadidi-Niaragh

  9. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Farhad Jadidi-Niaragh

Authors
  1. Narges Rostami
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  2. Afshin Nikkhoo
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  3. Amir Ajjoolabady
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  4. Gholamreza Azizi
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  5. Mohammad Hojjat-Farsangi
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  6. Ghasem Ghalamfarsa
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  7. Bahman Yousefi
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  8. Mehdi Yousefi
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  9. Farhad Jadidi-Niaragh
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Corresponding author

Correspondence to Farhad Jadidi-Niaragh.

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There was no funding.

Conflict of interest

None of the authors (NR, AN, AA, GA, MHF, GG, BY, MY, and FJN) have any conflict of interest to declare.

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Rostami, N., Nikkhoo, A., Ajjoolabady, A. et al. S1PR1 as a Novel Promising Therapeutic Target in Cancer Therapy. Mol Diagn Ther 23, 467–487 (2019). https://doi.org/10.1007/s40291-019-00401-5

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  • DOI: https://doi.org/10.1007/s40291-019-00401-5

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