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

Abstract 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...

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Main Authors: Tobias Ocklenburg, Fabian Neumann, Alexandra Wolf, Julia Vogel, Kirsten Göpelt, Melanie Baumann, Jennifer Baumann, Philip Kranz, Eric Metzen, Ulf Brockmeier
Format: Article
Language:English
Published: Nature Publishing Group 2021-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-86658-5
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spelling doaj-70c99fc6b9384a9d8053fe7ddefd89622021-04-04T11:31:21ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111210.1038/s41598-021-86658-5In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathwayTobias Ocklenburg0Fabian Neumann1Alexandra Wolf2Julia Vogel3Kirsten Göpelt4Melanie Baumann5Jennifer Baumann6Philip Kranz7Eric Metzen8Ulf Brockmeier9Institut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenInstitut Für Physiologie, Universität Duisburg-EssenDepartment of Neurology, University Hospital EssenAbstract 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.https://doi.org/10.1038/s41598-021-86658-5
collection DOAJ
language English
format Article
sources DOAJ
author Tobias Ocklenburg
Fabian Neumann
Alexandra Wolf
Julia Vogel
Kirsten Göpelt
Melanie Baumann
Jennifer Baumann
Philip Kranz
Eric Metzen
Ulf Brockmeier
spellingShingle Tobias Ocklenburg
Fabian Neumann
Alexandra Wolf
Julia Vogel
Kirsten Göpelt
Melanie Baumann
Jennifer Baumann
Philip Kranz
Eric Metzen
Ulf Brockmeier
In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
Scientific Reports
author_facet Tobias Ocklenburg
Fabian Neumann
Alexandra Wolf
Julia Vogel
Kirsten Göpelt
Melanie Baumann
Jennifer Baumann
Philip Kranz
Eric Metzen
Ulf Brockmeier
author_sort Tobias Ocklenburg
title In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
title_short In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
title_full In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
title_fullStr In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
title_full_unstemmed In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway
title_sort in oxygen-deprived tumor cells erp57 provides radioprotection and ensures proliferation via c-myc, plk1 and the akt pathway
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-03-01
description Abstract 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.
url https://doi.org/10.1038/s41598-021-86658-5
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