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Glutathione Peroxidase 2, a Selenoprotein Exhibiting a Dual Personality in Preventing and Promoting Cancer

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Selenium

Abstract

GPx2 is mainly expressed in the intestine but also up-regulated in several cancer types. Being a selenoprotein and a target of the transcription factor Nrf2, it was first proposed to protect from tumor development. However, it turned out that the picture is much more complex. GPx2 is not only regulated by Nrf2, but also by β-catenin and the Wnt pathway, ΔNp63, and NKX3.1, which are pathways involved in the regulation of proliferative and survival processes. Accordingly, GPx2 was also found to enhance proliferation and to inhibit apoptosis. These are important functions required to maintain homeostasis in the healthy intestine. However, acting in cancer cells, they will promote the progression of the disease, as confirmed in several models of cancer and by a decrease of tumor development in Gpx2 knockout mice. In contrast, if carcinogenesis is driven by inflammation, GPx2 rather acts protective. The recent identification of STAT3 as an additional transcription factor inducing GPx2 might explain the up-regulation of GPx2 in inflammation and point to a role of GPx2 in tissue regeneration and wound healing. Thus, in accordance with the different pathways regulating its expression, GPx2 can act anti- and pro-carcinogenic depending on the tumor model and stage of cancer. Whereas it can inhibit initiation, it supports tumor growth, if a cancer cell has been established.

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Author information

Authors and Affiliations

  1. German Institute of Human Nutrition Potsdam-Rehbrücke, 14558, Nuthetal, Germany

    Regina Brigelius-Flohé & Anna P. Kipp

Authors
  1. Regina Brigelius-Flohé
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  2. Anna P. Kipp
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Corresponding author

Correspondence to Regina Brigelius-Flohé .

Editor information

Editors and Affiliations

  1. Mouse Cancer Genetics Program, National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA

    Dolph L. Hatfield

  2. Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Nordrhein-Westfalen, Germany

    Ulrich Schweizer

  3. Department of Biological Sciences, Towson University, Towson, Maryland, USA

    Petra A. Tsuji

  4. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts, USA

    Vadim N. Gladyshev

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Brigelius-Flohé, R., Kipp, A.P. (2016). Glutathione Peroxidase 2, a Selenoprotein Exhibiting a Dual Personality in Preventing and Promoting Cancer. In: Hatfield, D., Schweizer, U., Tsuji, P., Gladyshev, V. (eds) Selenium. Springer, Cham. https://doi.org/10.1007/978-3-319-41283-2_38

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