University of Oulu

Kozlova, Nina, Marieke Wottawa, Dörthe Magdalena Katschinski, Glen Kristiansen, Thomas Kietzmann, Nina Kozlova, Marieke Wottawa, Dörthe Magdalena Katschinski, Glen Kristiansen, and Thomas Kietzmann. 2016. "Hypoxia-Inducible Factor Prolyl Hydroxylase 2 (PHD2) is a Direct Regulator of Epidermal Growth Factor Receptor (EGFR) Signaling in Breast Cancer." Oncotarget 8 (6): 9885-9898. doi:10.18632/oncotarget.14241

Hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is a direct regulator of epidermal growth factor receptor (EGFR) signaling in breast cancer

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Author: Kozlova, Nina1; Wottawa, Marieke2; Katschinski, Dörthe Magdalena2;
Organizations: 1Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland
2Institute of Cardiovascular Physiology, University Medical Center, Georg-August-University Göttingen, 37073 Göttingen, Germany
3Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.5 MB)
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Language: English
Published: Impact Journals, 2016
Publish Date: 2017-02-27


Clinical studies in breast cancer suggest important associations between intratumoral hypoxia, the upregulation of epidermal growth factor receptor (EGFR or HER1), hypoxia-inducible factor 1α (HIF-1α), and reduced patient survival. However, direct molecular links between EGFR and the hypoxia signaling system are not yet established. Since the oxygen sensor hypoxia-inducible factor prolyl hydroxylase 2 (PHD2) is considered to be the main HIF-1α regulator, we hypothesized that PHD2 and EGFR may be interconnected at the molecular level. By analyzing samples from 313 breast cancer patients, we found that EGFR is a first clinicopathological parameter positively correlating with PHD2. Mechanistically, we identified PHD2 as a direct binding partner of EGFR and show that PHD2 regulates EGFR stability as well as its subsequent signaling in breast carcinoma cells. Overall, we introduce for the first time the direct crosstalk between the oxygen sensor PHD2 and EGFR-mediated tumorigenesis in breast cancer.

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Series: Oncotarget
ISSN: 1949-2553
ISSN-E: 1949-2553
ISSN-L: 1949-2553
Volume: 8
Issue: 6
Pages: 9885 - 9898
DOI: 10.18632/oncotarget.14241
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by Federation of European Biochemical Societies (FEBS), Finnish Center of International Mobility (CIMO), Biocenter Oulu, University of Oulu, Jane and Aatos Erkko Foundation, Finnish Academy of Sciences, and the Sigrid Juselius Foundation.
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