Selenium pp 451-462 | Cite as

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

  • Regina Brigelius-FlohéEmail author
  • Anna P. Kipp


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.


Apoptosis Cancer Dual role GPx2 Inflammation NKX3.1 Np63 Nrf2 Proliferation STAT Transcriptional regulation Wnt 


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Copyright information

© Springer Science+Business Media, LLC 2016

Authors and Affiliations

  1. 1.German Institute of Human Nutrition Potsdam-RehbrückeNuthetalGermany

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