Pawlak Magdalena, Kikulska Agnieszka, Wrzesinski Tomasz, Rausch Tobias, Kwias Zbigniew, Wilczynski Bartek, Benes Vladimir, Wesoly Joanna, Wilanowski Tomasz
Laboratory of Signal Transduction, Department of Cell Biology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
Faculty of Biology, Laboratory of High Throughput Technologies, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland.
Mol Carcinog. 2017 Nov;56(11):2414-2423. doi: 10.1002/mc.22682. Epub 2017 Jun 15.
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.
颗粒头样（GRHL）转录因子参与多种癌症已有充分记载。然而，它们在肾透明细胞癌（ccRCC）中的作用却鲜为人知。我们发现，其中两个因子GRHL1和GRHL2在ccRCC样本中的表达下调，且它们的表达与VHL基因的表达相关。这表明GRHL转录因子与最著名的肿瘤抑制因子之一之间存在功能联系。尽管GRHL基因在ccRCC中未发生突变，但这些基因中的一些单核苷酸多态性可能表明ccRCC发生风险增加和/或可用于评估患者预后并预测其对各种治疗形式的反应。在非致瘤性肾细胞系中沉默GRHL2表达会导致细胞增殖增加、对凋亡的抗性增强，以及参与ccRCC发病机制的某些选定蛋白水平发生变化。这些变化支持了GRHL2作为ccRCC抑制因子的潜在作用。
