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Sigma1 Pharmacology in the Context of Cancer

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Sigma Proteins: Evolution of the Concept of Sigma Receptors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 244))

Abstract

Sigma1 (also known as sigma-1 receptor, Sig1R, σ1 receptor) is a unique pharmacologically regulated integral membrane chaperone or scaffolding protein. The majority of publications on the subject have focused on the neuropharmacology of Sigma1. However, a number of publications have also suggested a role for Sigma1 in cancer. Although there is currently no clinically used anti-cancer drug that targets Sigma1, a growing body of evidence supports the potential of Sigma1 ligands as therapeutic agents to treat cancer. In preclinical models, compounds with affinity for Sigma1 have been reported to inhibit cancer cell proliferation and survival, cell adhesion and migration, tumor growth, to alleviate cancer-associated pain, and to have immunomodulatory properties. This review will highlight that although the literature supports a role for Sigma1 in cancer, several fundamental questions regarding drug mechanism of action and the physiological relevance of aberrant SIGMAR1 transcript and Sigma1 protein expression in certain cancers remain unanswered or only partially answered. However, emerging lines of evidence suggest that Sigma1 is a component of the cancer cell support machinery, that it facilitates protein interaction networks, that it allosterically modulates the activity of its associated proteins, and that Sigma1 is a selectively multifunctional drug target.

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Acknowledgements

We thank Drs. Paul McGonigle and James Barrett and members of the Kim Lab for critical reading of this manuscript. We thank John Vaillancourt for technical support in performing the SIGMAR1 gene expression analysis in Fig. 1.

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  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA, USA

    Felix J. Kim & Christina M. Maher

  2. Sidney Kimmel Cancer Center, Philadelphia, PA, USA

    Felix J. Kim

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Correspondence to Felix J. Kim .

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  1. Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Felix J. Kim

  2. Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Gavril W. Pasternak

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Kim, F.J., Maher, C.M. (2017). Sigma1 Pharmacology in the Context of Cancer. In: Kim, F., Pasternak, G. (eds) Sigma Proteins: Evolution of the Concept of Sigma Receptors. Handbook of Experimental Pharmacology, vol 244. Springer, Cham. https://doi.org/10.1007/164_2017_38

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