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The EMT-activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but is predictive of survival

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posted on 2023-01-10, 16:54 authored by Sophie Rae, Cathy Spillane, Gordon Blackshields, Stephen MaddenStephen Madden, Joanne Keenan, Britta Stordal
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.


Marie Curie International Incoming Fellowship and a Career Integration Grant from the European Union FP7 programme

Irish Cancer Society Postdoctoral Fellowship

Middlesex University



The original article is available at https://link.springer.com/

Published Citation

Rae S. et al. The EMT-activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but is predictive of survival. Hum Cell. 2022;35(5):1547-1559

Publication Date

6 July 2022

PubMed ID



  • Data Science Centre

Research Area

  • Cancer
  • Neurological and Psychiatric Disorders
  • Gynaecology, Obstetrics and Perinatal Health




  • Published Version (Version of Record)