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. 2022 Jun 8;17(2):123.
doi: 10.3892/mco.2022.2556. eCollection 2022 Aug.

ZEB1 induces N-cadherin expression in human glioblastoma and may alter patient survival

Hanna Gött  1 , Jasmin Nagl  1 , Frederike Hagedorn  2 , Samuel Thomas  1 , Frank P Schwarm  1 , Eberhard Uhl  1 , Malgorzata A Kolodziej  1
Affiliations

ZEB1 induces N-cadherin expression in human glioblastoma and may alter patient survival

Hanna Gött et al. Mol Clin Oncol. .

Abstract

The present study investigated the expression of epithelial-mesenchymal transition (EMT)-related factors zinc finger E-box-binding homeobox 1 (ZEB1), cadherin-1 (CDH1), cadherin-2 (CDH2) and the cell cycle modulating kinase cyclin-dependent kinase 1 (CDK1) in human glioblastoma (GBM) compared to normal brain tissue, as well as whether the levels of expression were associated with the overall and progression-free survival of the GBM patients. In 44 GBM and five normal brain tissue specimens, the expression levels of ZEB1, CDH1, CDH2 and CDK1 were evaluated by real-time PCR and immunostaining, and the results were correlated with clinical data. The expression levels of all investigated genes as detected by immunostaining were significantly higher in the GBM when compared to the normal brain tissues. There was no influence on survival. A linear correlation between ZEB1 and CDH2 and CDK1 expression was observed in GBM. Moreover, ZEB1 was involved in EMT (e.g., signaling in human GBM) and high ZEB1 levels were linked to an aberrant cell cycle processing, marked by CDK1 overexpression.

Keywords: CDK1; ZEB1; cancer; cell cycle; epithelial to mesenchymal transition; gene expression; glioblastoma; molecular oncology; tumor progression.

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Conflict of interest statement

The authors declare that they have no competing or conflicting interests. MAK, HG, JN, FPS, FH, EU and ST confirm disclosing all financial and non-financial competing interests for myself and on behalf of my co-authors.

Figures

Figure 1
Figure 1
(A) CDH1 expression in GBM. (B) CDH1 expression in NBT. (C) CDH2 expression in GBM. (D) CDH2 expression in NBT. CDK1 was stained with higher intensity in (E) human GBM than in (F) NBT. ZEB1 expression was also significantly higher in (G) GBM than in (H) NBT. Although nuclear staining was observed no quantification was performed during the original investigations. As the project was already closed, no retroactive quantification was possible. The green lines indicate a measurement of 1 µm; further insertion of a scale bar is unfortunately not possible due to the used software. CDHI, cadherin-1; CDH2, cadherin-1; GBM, glioblastoma; NBT, normal brain tissue; CDK1, cyclin-dependent kinase 1; ZEB1, zinc finger E-box-binding homeobox 1.
Figure 2
Figure 2
The IHC-score of ZEB1 (***P<0.001), CDK1 (***P<0.001), E-cadherin (***P<0.001) and N-cadherin (**P=0.001) were significantly overexpressed in human GBM compared to NBT specimens. CDK1, cyclin-dependent kinase 1; ZEB1, zinc finger E-box-binding homeobox 1; GBM, glioblastoma; NBT, normal brain tissue.
Figure 3
Figure 3
Expression of ZEB1, CDK1, CDH1 and CDH2 in GBM compared to NBT at the mRNA level. Only CDK1 (**P=0.001) exhibited significantly higher expression in the GBM compared to the NBT specimens. CDHI, cadherin-1; CDH2, cadherin-1; GBM, glioblastoma; NBT, normal brain tissue; CDK1, cyclin-dependent kinase 1; ZEB1, zinc finger E-box-binding homeobox 1.
Figure 4
Figure 4
Correlation matrix of all investigated genes at the protein (A) and at the mRNA expression level (B).
See this image and copyright information in PMC

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