The EMT-activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but is predictive of survival.
Cisplatin
EMT
Ovarian cancer
Paclitaxel
ZEB1
Journal
Human cell
ISSN: 1749-0774
Titre abrégé: Hum Cell
Pays: Japan
ID NLM: 8912329
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
19
04
2022
accepted:
24
06
2022
pubmed:
7
7
2022
medline:
17
8
2022
entrez:
6
7
2022
Statut:
ppublish
Résumé
The IGROVCDDP cisplatin-resistant ovarian cancer cell line is an unusual model, as it is also cross-resistant to paclitaxel. IGROVCDDP, therefore, models the resistance phenotype of serous ovarian cancer patients who have failed frontline platinum/taxane chemotherapy. IGROVCDDP has also undergone epithelial-mesenchymal transition (EMT). We aim to determine if alterations in EMT-related genes are related to or independent from the drug-resistance phenotypes. EMT gene and protein markers, invasion, motility and morphology were investigated in IGROVCDDP and its parent drug-sensitive cell line IGROV-1. ZEB1 was investigated by qPCR, Western blotting and siRNA knockdown. ZEB1 was also investigated in publicly available ovarian cancer gene-expression datasets. IGROVCDDP cells have decreased protein levels of epithelial marker E-cadherin (6.18-fold, p = 1.58e-04) and higher levels of mesenchymal markers vimentin (2.47-fold, p = 4.43e-03), N-cadherin (4.35-fold, p = 4.76e-03) and ZEB1 (3.43-fold, p = 0.04). IGROVCDDP have a spindle-like morphology consistent with EMT. Knockdown of ZEB1 in IGROVCDDP does not lead to cisplatin sensitivity but shows a reversal of EMT-gene signalling and an increase in cell circularity. High ZEB1 gene expression (HR = 1.31, n = 2051, p = 1.31e-05) is a marker of poor overall survival in high-grade serous ovarian-cancer patients. In contrast, ZEB1 is not predictive of overall survival in high-grade serous ovarian-cancer patients known to be treated with platinum chemotherapy. The increased expression of ZEB1 in IGROVCDDP appears to be independent of the drug-resistance phenotypes. ZEB1 has the potential to be used as biomarker of overall prognosis in ovarian-cancer patients but not of platinum/taxane chemoresistance.
Identifiants
pubmed: 35794446
doi: 10.1007/s13577-022-00744-y
pii: 10.1007/s13577-022-00744-y
pmc: PMC9374625
doi:
Substances chimiques
Platinum Compounds
0
ZEB1 protein, human
0
Zinc Finger E-box-Binding Homeobox 1
0
Paclitaxel
P88XT4IS4D
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1547-1559Informations de copyright
© 2022. The Author(s).
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