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

Ocklenburg, Tobias; Neumann, Fabian; Wolf, Alexandra; Vogel, Julia; Göpelt, Kirsten; Baumann, Melanie; Baumann, Jennifer; Kranz, Philip; Metzen, Eric; Brockmeier, Ulf

doi:10.1038/s41598-021-86658-5

Artikel / Aufsatz Di., 30. März. 2021 CC BY 4.0

Veröffentlicht

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

Ocklenburg, Tobias ; Neumann, Fabian ; Wolf, Alexandra ; Vogel, Julia ; Göpelt, Kirsten ; Baumann, Melanie ; Baumann, Jennifer ; Kranz, Philip ; Metzen, Eric ; 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.

Vorschau

Einordnung

Datum der Veröffentlichung:

30.03.2021

URN:

urn:nbn:de:hbz:465-20240828-094701-1

DOI:

10.1038/s41598-021-86658-5

Sprache:

Englisch

Ressourcentyp:

Text

Schlagwörter:

Biochemistry; Cancer; Cell biology; Molecular biology

Kollektion:

E-Publikationen

Sachgruppen der Deutschen Nationalbibliographie:

610 Medizin, Gesundheit

Einrichtung:

Medizinische Fakultät, Universitätsklinikum Essen, Institut für Physiologie

Einrichtung:

Medizinische Fakultät, Universitätsklinikum Essen, Klinik für Neurologie

Förderung:

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.

Informationen zur Erstveröffentlichung:

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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