In oxygen-deprived tumor cells ERp57 provides radioprotection and ensures proliferation via c-Myc, PLK1 and the AKT pathway.
Sci Rep
; 11(1): 7199, 2021 03 30.
Article
em En
| MEDLINE
| ID: mdl-33785835
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-myc
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Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
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Neoplasias do Colo
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Proteínas de Ciclo Celular
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Isomerases de Dissulfetos de Proteínas
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Proteínas Proto-Oncogênicas c-akt
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Hipóxia Tumoral
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha