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In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway

GND
1236931645
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Ocklenburg, Tobias;
GND
1224827325
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Neumann, Fabian;
GND
1177826291
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Wolf, Alexandra;
GND
1236345754
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Vogel, Julia;
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Göpelt, Kirsten;
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Baumann, Melanie;
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Baumann, Jennifer;
GND
1160734437
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Kranz, Philip;
GND
114398968
ORCID
0000-0002-2740-3219
LSF
50408
Affiliation
Institut Für Physiologie, Universität Duisburg-Essen, Duisburg, Germany
Metzen, Eric;
GND
131907352
LSF
63903
Affiliation
Department of Neurology, University Hospital Essen, Essen, Germany
Brockmeier, Ulf
The disulfide isomerase ERp57, originally found in the endoplasmic reticulum, is located in multiple cellular compartments, participates in diverse cell functions and interacts with a huge network of binding partners. It was recently suggested as an attractive new target for cancer therapy due to its critical role in tumor cell proliferation. Since a major bottleneck in cancer treatment is the occurrence of hypoxic areas in solid tumors, the role of ERp57 in cell growth was tested under oxygen depletion in the colorectal cancer cell line HCT116. We observed a severe growth inhibition when ERp57 was knocked down in hypoxia (1% O2 ) as a consequence of downregulated c-Myc, PLK1, PDPK1 (PDK1) and AKT (PKB). Further, irradiation experiments revealed also a radiosensitizing effect of ERp57 depletion under oxygen deprivation. Compared to ERp57, we do not favour PDPK1 as a suitable pharmaceutical target as its efficient knockdown/chemical inhibition did not show an inhibitory effect on proliferation.

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Date Issued:
30.03.2021
URN:
urn:nbn:de:hbz:465-20240828-094701-1
DOI:
10.1038/s41598-021-86658-5
Language:
English
Type of Resource:
Text
Keywords:
Biochemistry; Cancer; Cell biology; Molecular biology
Collection:
E-Publications
Subject categories of the Deutsche Nationalbibliografie:
610 Medical sciences Medicine
Hosting institution:
Faculty of Medicine, Essen University Hospital, Institute of Physiology
Hosting institution:
Faculty of Medicine, Essen University Hospital, Clinic for Neurology
funding:

The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.

This study was funded by the research training group GRK1739 of the Deutsche Forschungs gemeinschaft.

Open Access funding enabled and organized by Projekt DEAL.

Info on primary publication:

Ocklenburg, T., Neumann, F., Wolf, A. et al. In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway. Sci Rep 11, 7199 (2021). https://doi.org/10.1038/s41598-021-86658-5

Published 30 March 2021

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Version of Record / Verlagsversion

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