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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Autores principales:	Tobias Ocklenburg, Fabian Neumann, Alexandra Wolf, Julia Vogel, Kirsten Göpelt, Melanie Baumann, Jennifer Baumann, Philip Kranz, Eric Metzen, Ulf Brockmeier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70c99fc6b9384a9d8053fe7ddefd8962
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spelling	oai:doaj.org-article:70c99fc6b9384a9d8053fe7ddefd89622021-12-02T14:23:18ZIn oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway10.1038/s41598-021-86658-52045-2322https://doaj.org/article/70c99fc6b9384a9d8053fe7ddefd89622021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86658-5https://doaj.org/toc/2045-2322Abstract 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.Tobias OcklenburgFabian NeumannAlexandra WolfJulia VogelKirsten GöpeltMelanie BaumannJennifer BaumannPhilip KranzEric MetzenUlf BrockmeierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Tobias Ocklenburg Fabian Neumann Alexandra Wolf Julia Vogel Kirsten Göpelt Melanie Baumann Jennifer Baumann Philip Kranz Eric Metzen Ulf Brockmeier
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 Portfolio
publishDate	2021
url	https://doaj.org/article/70c99fc6b9384a9d8053fe7ddefd8962
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In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway

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