scholarly journals SOX17 Antagonizes the WNT Signaling Pathway and is Epigenetically Inactivated in Clear-Cell Renal Cell Carcinoma

2021 ◽  
Vol Volume 14 ◽  
pp. 3383-3394
Author(s):  
Lu Wang ◽  
Zhe Wang ◽  
Yuze Zhu ◽  
Shutao Tan ◽  
Xiaonan Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma

scholarly journals Porcupine Inhibitor LGK974 Downregulates the Wnt Signaling Pathway and Inhibits Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Jianyi Li ◽  
Guangzhen Wu ◽  
Yingkun Xu ◽  
Jiatong Li ◽  
Ningke Ruan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma ◽  
Wnt Proteins

Targeted therapy for kidney cancer has achieved significant clinical results. However, because most patients who use targeted therapy will develop drug resistance, we still need to constantly explore new therapeutic targets. Although porcupine (PORCN) as a palmitoyltransferase plays a crucial role in the activation and secretion of Wnt proteins and affects the activity of the Wnt signaling pathway, little is known about the role of PORCN in clear cell renal cell carcinoma (ccRCC). We found that PORCN is highly expressed in renal cancer cell lines and patients with renal cell carcinoma with high expression of PORCN have a poor prognosis. Pathway analysis of PORCN and its related proteins showed that PORCN played a role through the Wnt signaling pathway, and there was a strong coexpression relationship between PORCN and Wnt proteins. Therefore, PORCN may be a potential and effective target for ccRCC. In the present study, we found that LGK974 could inhibit proliferation and colony formation and induce apoptosis in ccRCC cells. We also found that LGK974 could inhibit the migration and invasion of renal cell carcinoma and reduce the expression of mesenchymal markers. After treatment with LGK974, the expression level of β-catenin, a key protein in the classical Wnt pathway, was significantly decreased, and the expression levels of the target genes cyclin D1, c-Myc, MMP9, and MMP2 in the Wnt signaling pathway were also significantly decreased, which represented a significant decrease in the activity of the Wnt signaling pathway. At the same time, the cycle of renal cancer cells was significantly blocked. In conclusion, our results indicate that LGK974 could significantly inhibit the progression of renal cancer cells in a safe concentration range, so PORCN may be a safe and effective target for patients with renal cancer.

scholarly journals Kindlin-2 promotes clear cell renal cell carcinoma progression through the Wnt signaling pathway

2017 ◽  
Vol 38 (3) ◽  
pp. 1551-1560 ◽  
Author(s):  
Muhan Li ◽  
Xuelian Pei ◽  
Guoliang Wang ◽  
Jun Zhan ◽  
Juan Du ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Wnt Signaling ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Cell Renal Cell Carcinoma

scholarly journals A Novel miRNA-Based Model Can Predict the Prognosis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Jiyue Wu ◽  
Feilong Zhang ◽  
Jiandong Zhang ◽  
Zejia Sun ◽  
Changzhen Hao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Wnt Signaling Pathway ◽  
Functional Enrichment ◽  
Hippo Signaling ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal malignant cancer, whose survival rate and quality of life of patients are still not satisfactory. Nevertheless, the TNM staging system currently used in clinical cannot make accurate survival predictions and precise treatment decisions for ccRCC patients. Therefore, there is an urgent need for more reliable biomarkers to identify high-risk subgroups of ccRCC patients to guide timely intervention and treatment. Recently, MiRNAs have been shown to be closely related to the procession of a variety of tumors, and they have high stability in various tissues, which makes them suggested to have the potential as a prognostic biomarker of ccRCC. In this study, by analyzing and processing the miRNAs expression profile of ccRCC patients from the TCGA database, we finally constructed an excellent miRNAs signature and verified it through a variety of methods. In order to build a more accurate and reliable clinical predictive model, we integrated the miRNAs signature with other prognostic-related clinical parameters to construct a nomogram. Functional enrichment analysis showed that miRNAs in the signature may regulate the genes involved in the Hippo signaling pathway, Tight junction, and Wnt signaling pathway to cause different prognoses of ccRCC patients, which may provide a reference for subsequent basic research and targeted therapy. To conclude, our study constructed a useful miRNAs signature, which allows the prognosis stratification for ccRCC patients and thereby guides the timely and effective interventions on high-risk patients. At the same time, this study also found the potential biological pathways involved in the procession of ccRCC.

scholarly journals ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Shenglin Gao ◽  
Lei Gao ◽  
Simin Wang ◽  
Xiaokai Shi ◽  
Chuang Yue ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Clear Cell ◽  
Invasion Assay ◽  
Cell Renal Cell Carcinoma ◽  
Atf3 Expression

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignant cancers in East Asia, with high incidence and mortality. Accumulating evidence has shown that ATF3 is associated with tumor progression.MethodsUsing qPCR, the expression of ATF3 was detected in 93 patients with ccRCC, including 24 paired normal and tumor tissues, which were used to further compare ATF3 expression through western blotting and immunohistochemistry. Lentivirus was used for the overexpression or knockdown of ATF3, and the consequent alteration in function was analyzed through CCK8 assay, colony formation assay, wound healing assay, invasion assay, and flow cytometry. The potential mechanism affected by ATF3 was analyzed through gene set enrichment analysis (GSEA) and verified using western blotting, invasion assay, or immunofluorescence staining. Furthermore, a xenograft mouse model was used to assess the function of ATF3 in vivo.ResultsATF3 expression was significantly decreased in ccRCC compared to that in adjacent normal tissues. Through gain- and loss-of-function experiments performed in an in vitro assay, we found that ATF3 could regulate ccRCC cell proliferation, cycle progression, migration, and invasion. In the in vivo study, the xenograft mouse model revealed that ATF3 overexpression can inhibit the growth of ccRCC. Moreover, the mechanism analysis showed that suppression of ATF3 could lead to an increase the expression of β-catenin and promote β-catenin transfer to the nucleus, and might be affected by EGFR/AKT/GSK3β signaling.ConclusionATF3 could be utilized as an independent protective factor to inhibit the progression of ccRCC. Potential treatment strategies for ccRCC include targeting the ATF3/EGFR/AKT/GSK3β/β−catenin signaling pathway.

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