Potential protective role of Grainyhead-like genes in the development of clear cell renal cell carcinoma
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Updated: Mar 1, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Magdalena Pawlak1, Agnieszka Kikulska1, Tomasz Wrzesinski2
1Laboratory of Signal Transduction, Department of Cell Biology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Abstract:
The involvement of Grainyhead-like (GRHL) transcription factors in various cancers is well documented. However, little is known about their role in clear cell renal cell carcinoma (ccRCC). We discovered that the expression of two of these factors-GRHL1 and GRHL2-are downregulated in ccRCC samples, and their expression is correlated with the expression of VHL gene. This suggests a functional link between the GRHL transcription factors and one of the best known tumor suppressors. Although the GRHL genes are not mutated in ccRCC, some of the single nucleotide polymorphisms in these genes may indicate an increased risk of ccRCC development and/or may allow to assess patients' prognoses and predict their responses to various forms of therapy. Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of ccRCC. These changes support the potential role for GRHL2 as a suppressor of ccRCC.
Insights
Grainyhead-like transcription factors GRHL1 and GRHL2 are downregulated in clear cell renal cell carcinoma (ccRCC). Reduced GRHL2 expression promotes ccRCC cell proliferation and apoptosis resistance, suggesting its tumor-suppressive role.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Grainyhead-like (GRHL) transcription factors are implicated in various cancers.
- The specific role of GRHL factors in clear cell renal cell carcinoma (ccRCC) remains largely unexplored.
Purpose of the Study:
- To investigate the expression and function of GRHL1 and GRHL2 in ccRCC.
- To explore the potential link between GRHL factors and VHL gene expression in ccRCC.
- To assess the prognostic and therapeutic implications of GRHL gene polymorphisms in ccRCC.
Main Methods:
- Analysis of GRHL1 and GRHL2 expression in ccRCC samples.
- Correlation analysis between GRHL and VHL gene expression.
- Assessment of GRHL gene single nucleotide polymorphisms (SNPs) for ccRCC risk and prognosis.
- In vitro silencing of GRHL2 in a kidney cell line to study its functional impact.
Main Results:
- GRHL1 and GRHL2 expression is downregulated in ccRCC tissues.
- GRHL expression levels correlate with VHL gene expression.
- GRHL gene SNPs may be associated with ccRCC risk, prognosis, and therapy response.
- GRHL2 silencing in kidney cells leads to increased proliferation, apoptosis resistance, and altered protein levels relevant to ccRCC pathogenesis.
Conclusions:
- GRHL1 and GRHL2 are downregulated in ccRCC, suggesting a tumor-suppressive role.
- A functional link exists between GRHL factors and the VHL tumor suppressor.
- GRHL2 acts as a potential suppressor of ccRCC, with implications for patient prognosis and treatment.
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