Wnt Signaling in Renal Cell Carcinoma

Xu, Qi-Zheng; Krause, Mirja; Samoylenko, Anatoly; Vainio, Seppo

doi:10.3390/cancers8060057

Cited by 82 publications

(80 citation statements)

References 105 publications

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“…Recent studies have also shown aberrant signal transduction of WNT/β-catenin is correlated with an aggressive phenotype [15, 28, 29]. However, the exact mechanisem of WNT/β-catenin classical pathway involved in RCC progression is still under investigation.…”

Section: Discussionmentioning

confidence: 99%

Reduced E-cadherin facilitates renal cell carcinoma progression by WNT/β-catenin signaling activation

et al. 2017

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Reduced expression of E-cadherin was observed in renal cell carcinoma (RCC). However, its potential clinical value and correlation with WNT/β-catenin signaling in RCC progression was still unclear. Immunohistochemical staining was performed in RCC tissue microarray to examine the expression status and prognosis value of E-cadherin and β-catenin. The potential role of E-cadherin in β-catenin translocation was analyzed with immunobloting assays. A significant negative correlation was observed between E-cadherin and β-catenin expression in RCC tissues. E-cadherin inhibits β-catenin translocation from membrane to cytoplasm in RCC tissues, which was an important step for WNT/β-catenin signaling. Reduced E-cadherin expression was associated with poor prognosis. More importantly, E-cadherin-/β-catenin+ was an independent detrimental factor for survival estimation of RCC patients. Reduced E-cadherin expression in RCC promoted cancer progression via WNT/β-catenin signaling pathway activation. E-cadherin/β-catenin provides a valuable prognosis marker for RCC, which may be an effective target for RCC therapy.

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Section: Discussionmentioning

confidence: 99%

Reduced E-cadherin facilitates renal cell carcinoma progression by WNT/β-catenin signaling activation

et al. 2017

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“…Although the binding partner of DKK-3 on the cell surface remains to be elucidated, these findings assist in clarifying the anti-cancer mechanisms of extracellular DKK-3. The Wnt signaling pathway serves an important role in the carcinogenesis and the progression of renal cell carcinoma (23), and the in vivo tumor-suppressive effects of the recombinant full length DKK-3 protein were previously demonstrated in the RENCa tumor model of murine renal carcinoma (24). Therefore, recombinant DKK-3 protein may be a promising agent for treating renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Exogenous DKK‑3/REIC inhibits Wnt/β‑catenin signaling and cell proliferation in human kidney cancer KPK1

Sadahira

Kinoshita

et al. 2017

Oncol Lett

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Abstract. The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/β-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)β-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-β-catenin (activated form of β-catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/β-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/β-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/β-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/β-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-β-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-β-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-β-catenin and inhibits Wnt/β-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit the proliferation of KPK1 cells via inactivating Wnt/β-catenin signaling.

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“…Kidney cancer accounts for approximately 2–3% of all cancers worldwide each year, and renal cell carcinoma (RCC) is thought to be the most common type of kidney malignancy with a slight male predominance . The incidence of RCC has increased in most regions during recent decades, and the morbidity of this disease is consistently increasing annually . Nearly half of patients die within the first 5 years after diagnosis with this disease .…”

Section: Introductionmentioning

confidence: 99%

Quantitative Global Proteome and Lysine Succinylome Analyses Reveal the Effects of Energy Metabolism in Renal Cell Carcinoma

et al. 2018

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In light of the increasing incidence of renal cell carcinoma (RCC), its molecular mechanisms have been comprehensively explored in numerous recent studies. However, few studies focus on the influence of multi-factor interactions during the occurrence and development of RCC. This study aims to investigate the quantitative global proteome and the changes in lysine succinylation in related proteins, seeking to facilitate a better understanding of the molecular mechanisms underlying RCC. LC-MS/MS combined with bioinformatics analysis are used to quantitatively detect the perspectives at the global protein level. IP and WB analysis were conducted to further verify the alternations of related proteins and lysine succinylation. A total of 3,217 proteins and 1,238 lysine succinylation sites are quantified in RCC tissues, and 668 differentially expressed proteins and 161 differentially expressed lysine succinylation sites are identified. Besides, expressions of PGK1 and PKM2 at protein and lysine, succinylation levels are significantly altered in RCC tissues. Bioinformatics analysis indicates that the glycolysis pathway is a potential mechanism of RCC progression and lysine succinylation may plays a potential role in energy metabolism. These results can provide a new direction for exploring the molecular mechanism of RCC tumorigenesis.

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Wnt Signaling in Renal Cell Carcinoma

Cited by 82 publications

References 105 publications

Reduced E-cadherin facilitates renal cell carcinoma progression by WNT/β-catenin signaling activation

Reduced E-cadherin facilitates renal cell carcinoma progression by WNT/β-catenin signaling activation

Exogenous DKK‑3/REIC inhibits Wnt/β‑catenin signaling and cell proliferation in human kidney cancer KPK1

Quantitative Global Proteome and Lysine Succinylome Analyses Reveal the Effects of Energy Metabolism in Renal Cell Carcinoma

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