Advertisement

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
Chapter

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.

Keywords

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

References

  1. 1.
    R Brigelius-Flohé, M Maiorino 2013 Biochim Biophys Acta 1830:3289CrossRefPubMedGoogle Scholar
  2. 2.
    R Brigelius-Flohé, A Kipp 2009 Biochim Biophys Acta 1790:1555CrossRefPubMedGoogle Scholar
  3. 3.
    SC Tosatto et al 2008 Antioxid Redox Signal 10:1515CrossRefPubMedGoogle Scholar
  4. 4.
    A Banning et al 2008 Antioxid Redox Signal 10:1491CrossRefPubMedGoogle Scholar
  5. 5.
    K Wingler et al 1999 Eur J Biochem 259:149CrossRefPubMedGoogle Scholar
  6. 6.
    K Wingler et al 2000 Gastroenterology 119:420CrossRefPubMedGoogle Scholar
  7. 7.
    HY Cho et al 2002 Am J Respir Cell Mol Biol 26:42CrossRefPubMedGoogle Scholar
  8. 8.
    FF Chu et al 1993 J Biol Chem 268:2571PubMedGoogle Scholar
  9. 9.
    S Florian et al 2001 Free Radic Res 35:655CrossRefPubMedGoogle Scholar
  10. 10.
    H Komatsu et al 2001 J Histochem Cytochem 49:759CrossRefPubMedGoogle Scholar
  11. 11.
    D Pinto et al 2003 Genes Dev 17:1709CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    AP Kipp, MF Müller 2016 in Diversity of Selenium Functions in Health and Disease, R Brigelius-Flohé, H Sies Eds (CRC Press, Boca Raton) p 189Google Scholar
  13. 13.
    B Dannenmann et al 2015 Stem Cell Reports 4:886CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    K Blaschke et al 2013 Nature 500:222CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    IJ Baek et al 2011 Anat Histol Embryol 40:210CrossRefPubMedGoogle Scholar
  16. 16.
    T Sato, H Clevers 2013 Science 340:1190CrossRefPubMedGoogle Scholar
  17. 17.
    HC Clevers, CL Bevins 2013 Annu Rev Physiol 75:289CrossRefPubMedGoogle Scholar
  18. 18.
    A Banning et al 2005 Mol Cell Biol 25:4914CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    D Kluth et al 2007 Free Radic Biol Med 42:315CrossRefPubMedGoogle Scholar
  20. 20.
    F Hiller et al 2015 Inflamm Bowel Dis 21:2078CrossRefPubMedGoogle Scholar
  21. 21.
    A Singh et al 2006 Am J Respir Cell Mol Biol 35:639CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    JD Hayes et al 2010 Antioxid Redox Signal 13:1713CrossRefPubMedGoogle Scholar
  23. 23.
    T Suzuki, M Yamamoto 2015 Free Radic Biol Med 88:93CrossRefPubMedGoogle Scholar
  24. 24.
    LE Tebay et al 2015 Free Radic Biol Med 88:108CrossRefPubMedGoogle Scholar
  25. 25.
    K Itoh et al 1997 Biochem Biophys Res Commun 236:313CrossRefPubMedGoogle Scholar
  26. 26.
    A Lau et al 2008 Pharmacol Res 58:262CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    K Taguchi et al 2011 Genes Cells 16:123CrossRefPubMedGoogle Scholar
  28. 28.
    TW Kensler, N Wakabayashi 2010 Carcinogenesis 31:90CrossRefPubMedGoogle Scholar
  29. 29.
    R Brigelius-Flohé et al 2012 Int J Cell Biol 2012:486147CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    S Murakami, H Motohashi 2015 Free Radic Biol Med 88:168CrossRefPubMedGoogle Scholar
  31. 31.
    MF Müller et al 2013 PLoS One 8:e72055CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    A Kipp et al 2007 Biol Chem 388:1027CrossRefPubMedGoogle Scholar
  33. 33.
    AP Kipp et al 2012 Biochim Biophys Acta 1820:1588CrossRefPubMedGoogle Scholar
  34. 34.
    J Bollrath et al 2009 Cancer Cell 15:91CrossRefPubMedGoogle Scholar
  35. 35.
    TA Willson et al 2013 Inflamm Bowel Dis 19:512CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    G Pickert et al 2009 J Exp Med 206:1465CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    J Martitz et al 2015 Metallomics 7:1515CrossRefPubMedGoogle Scholar
  38. 38.
    CA Lindemans et al 2015 Nature 528:560CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    JC Pignon et al 2013 Proc Natl Acad Sci U S A 110:8105CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    A Yang et al 1998 Mol Cell 2:305CrossRefPubMedGoogle Scholar
  41. 41.
    W Yan, X Chen 2006 J Biol Chem 281:7856CrossRefPubMedGoogle Scholar
  42. 42.
    C Abate-Shen et al 2008 Differentiation 76:717CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    X Ouyang et al 2005 Cancer Res 65:6773CrossRefPubMedGoogle Scholar
  44. 44.
    PD Anderson et al 2012 J Clin Invest 122:1907CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    A Banning et al 2012 in Selenium: Its Molecular Biology and Role in Human Health, DL Hatfield et al Eds (Springer Science + Business Media, LLC, New York) p 271Google Scholar
  46. 46.
    JE Visvader 2011 Nature 469:314CrossRefPubMedGoogle Scholar
  47. 47.
    D Trachootham et al 2008 Antioxid Redox Signal 10:1343CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    J Walshe et al 2007 Cancer Res 67:4751CrossRefPubMedGoogle Scholar
  49. 49.
    S Florian et al 2010 Free Radic Biol Med 49:1694CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    SK Niture, AK Jaiswal 2012 J Biol Chem 287:9873CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    SO Rahaman et al 2002 Oncogene 21:8404CrossRefPubMedGoogle Scholar
  52. 52.
    RS Esworthy et al 2001 Am J Physiol Gastrointest Liver Physiol 281:G848PubMedGoogle Scholar
  53. 53.
    RS Esworthy et al 2005 J Nutr 135:740PubMedGoogle Scholar
  54. 54.
    RS Esworthy et al 2014 Free Radic Biol Med 68:315CrossRefPubMedGoogle Scholar
  55. 55.
    LM Coussens, Z Werb 2002 Nature 420:860CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    AA Te Velde et al 2008 Eur J Gastroenterol Hepatol 20:555CrossRefGoogle Scholar
  57. 57.
    AM Dittrich et al 2010 Eur Respir J 35:1148CrossRefPubMedGoogle Scholar
  58. 58.
    N Kaushal et al 2014 J Immunol 193:3683CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    A Mangerich et al 2012 Proc Natl Acad Sci U S A 109:E1820CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    K Yang et al 2008 Cancer Res 68:7313CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    B Sovran et al 2015 Inflamm Bowel Dis 21:531CrossRefPubMedGoogle Scholar
  62. 62.
    S Krehl et al 2012 Carcinogenesis 33:620CrossRefPubMedGoogle Scholar
  63. 63.
    R Brigelius-Flohé, L Flohé 2011 Antioxid Redox Signal 15:2335CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    MC Sobotta et al 2015 Nat Chem Biol 11:64CrossRefPubMedGoogle Scholar
  65. 65.
    A Seiler et al 2008 Cell Metab 8:237CrossRefPubMedGoogle Scholar
  66. 66.
    UH Gandhi et al 2014 Cancer Res 74:3890CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    MM Serewko et al 2002 Cancer Res 62:3759PubMedGoogle Scholar
  68. 68.
    EMF De Sousa et al 2013 Nat Med 19:614CrossRefGoogle Scholar
  69. 69.
    BL Emmink et al 2014 Cancer Res 74:6717CrossRefPubMedGoogle Scholar
  70. 70.
    IW Chang et al 2015 World J Urol 33:1777CrossRefPubMedGoogle Scholar
  71. 71.
    A Naiki-Ito et al 2007 Cancer Res 67:11353CrossRefPubMedGoogle Scholar
  72. 72.
    S Suzuki et al 2013 Toxicology 311:115CrossRefPubMedGoogle Scholar
  73. 73.
    A Banning et al 2008 Cancer Res 68:9746CrossRefPubMedGoogle Scholar
  74. 74.
    T Naiki et al 2014 Carcinogenesis 35:1962CrossRefPubMedGoogle Scholar
  75. 75.
    E Piskounova et al 2015 Nature 527:186CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    WJ Blot et al 1993 J Natl Cancer Inst 85:1483CrossRefPubMedGoogle Scholar
  77. 77.
    D Medina 1986 Adv Exp Med Biol 206:465PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2016

Authors and Affiliations

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

Personalised recommendations