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

Zhang, Xinqi; Yang, Mingxi; Shi, Hua; Hu, Jianxin; Wang, Yuanlin; Sun, Zhaolin; Xu, Shuxiong

doi:10.18632/oncotarget.15361

Cited by 37 publications

(32 citation statements)

References 35 publications

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“…High or preserved membranous E-cadherin-expression was significantly associated with both worse OS and worse CSS. This is a novel finding with regard to former studies reporting on an association with worse outcome and loss of membranous E-cadherin-expression [15][16][17].…”

Section: Discussionsupporting

confidence: 65%

“…Furthermore, some authors could also find a relationship between reduced E-cadherin expression and worse CSS [15,16] or RFS [26]. In some studies, no association between E-cadherin-expression and survival could be found [27].…”

Section: Discussionmentioning

confidence: 99%

“…Krabbe et al [18] could identify an association between reduced β-Catenin-expression and worse RFS and CSS, whereas there are several studies showing no association between β-Catenin-expression and survival [26,28]. Furthermore, there are several studies suggesting a worse prognostic effect of high cytoplasmic β-Catenin expression and worse survival [15,21,22].…”

Section: Discussionmentioning

confidence: 99%

“…Cell-cell connection molecules like E-cadherin and β-Catenin play a crucial role in this process. For RCC, it has been shown that the loss of membranous E-cadherinexpression is associated with adverse outcome [15][16][17]. Concerning β-Catenin-expression, the situation is more complex.…”

Section: Impact Of E-cadherin and β-Catenin As Prognostic Factor In Rmentioning

confidence: 99%

“…There is evidence that a decreased β-Cateninexpression is associated with worse outcome, displaying the epithelial-mesenchymal transition-process [18]. However, a stabilization and preservation of β-Catenin also promotes proliferation, migration, and invasion in RCC [19,20] and thus is associated with worse survival [15,21,22].…”

Section: Impact Of E-cadherin and β-Catenin As Prognostic Factor In Rmentioning

confidence: 99%

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Impact of E-Cadherin and β-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava

et al. 2019

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Purpose: Renal cell carcinoma (RCC) forming tumor thrombus (TT) of vena cava (VC) is characterized by poor prognosis. Nevertheless, the outcome of patients after radical surgery varies. To date only limited data concerning prognostic biomarkers in this RCC subgroup are available. Methods: Out of 159 patients with pT3b/c RCC, 95 patients without synchronous distant metastases at time of diagnosis were included in the study cohort. After immunohistochemical (IHC) evaluation of E-cadherin and β-Catenin expression, association with clinical, histopathological and survival was assessed by univariate analysis, multivariate analysis, and Kaplan-Meier-analysis. Cancer-specific survival (CSS) rates and overall survival (OS) rates were estimated using Kaplan-Meier analysis and compared using Log rank test. Results: We found a significant correlation between E-cadherin overexpression and initial lymph node metastasis (ρ = 0.300, p = 0.003), positive surgical margins (ρ = 0.210, p = 0.043), and the development of distant metastases (ρ = 0.258, p = 0.012). Furthermore, we observed a significant correlation of β-Catenin overexpression with higher tumor stage pT3c (ρ = 0.230, p = 0.028) and initial lymph node metastases (ρ = 0.236, p = 0.025). Survival analysis revealed a statistically significant association of both E-cadherin and β-Catenin overexpression with worse CSS (p < 0.001 and p = 0.007, respectively) and OS (p < 0.001 and p = 0.041, respectively). Multivariate analysis revealed initial lymph node metastasis as the only predictive factor for worse OS (HR 4.54, 95% CI 2.30–8.93; p < 0.001). E-Cadherin and β-Catenin expression failed to be significant in multivariable analysis for OS and CSS. Conclusions: In a large series of RCC with TT of VC high IHC expression of E-cadherin and β-Catenin was associated with initial lymph node metastasis and with both worse OS and worse CSS. This might help to identify patients at risk for recurrence who might benefit from adjuvant therapy or stricter follow-up.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Impact Of E-cadherin and β-Catenin As Prognostic Factor In Rmentioning

confidence: 99%

Section: Impact Of E-cadherin and β-Catenin As Prognostic Factor In Rmentioning

confidence: 99%

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Impact of E-Cadherin and β-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava

et al. 2019

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Redox‐sensitive signaling pathways in renal cell carcinoma

et al. 2021

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Renal cell carcinoma (RCC) is one of the most lethal urological cancers, highly resistant to chemo and radiotherapy. Obesity and smoking are the best-known risk factors of RCC, both related to oxidative stress presence, suggesting a significant role in RCC development and maintenance. Surgical resection is the treatment of choice for localized RCC; however, this neoplasia is hardly diagnosable at its initial stages, occurring commonly in late phases and even when metastasis is already present. Systemic therapies are the option against RCC in these more advanced stages, such as cytokine therapy or a combination of tyrosine kinase inhibitors with immunotherapies; nevertheless, these strategies are still insufficient. A field poorly analyzed in this neoplasia is the status of cell

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FSCN1 predicts survival and is regulated by a PI3K‐dependent mechanism in renal cell carcinoma

Zhang

Zhao

Duan

et al. 2018

Journal Cellular Physiology

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While overexpression of FSCN1 is reported in several cancers, the prognostic significance of FSCN1 in renal cell carcinoma (RCC) and the molecular mechanisms involved remain largely unclear. We retrospectively enrolled 194 patients with non-metastatic clear-cell RCC undergoing nephrectomy in our center between 2008 and 2011. FSCN1 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and survival were evaluated. Functional effects of a modulated FSCN1 expression were analyzed with regard to invasion in RCC cell lines and metastasis in vivo. Here, we reported that FSCN1 was up-regulated in RCC tissues compared to non-tumor tissues, and associated with poor overall survival and recurrence-free survival. Its expression was not associated with age, tumor size, and clinical TNM stage. The incorporation of FSCN1 into the T stage and histologic grade would help to refine individual risk stratification. Preclinical studies using multiple RCC cells and orthotopic xenografts mice model indicated that FSCN1 could promote RCC cell invasion in vitro, and metastasis in vivo. Mechanistically, overexpression of FSCN1 led to an up-regulation of MMP9 and N-Cadherin. Notably, treating RCC cells with PI3 K/AKT inhibitors or knockdown GSK-3β decreased the expression of FSCN1, and then attenuated RCC invasion. Together, our results demonstrate that FSCN as an oncogene is a potential novel prognostic biomarker for RCC patients after nephrectomy, and can promote RCC metastasis.

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

Cited by 37 publications

References 35 publications

Impact of E-Cadherin and β-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava

Impact of E-Cadherin and β-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava

Redox‐sensitive signaling pathways in renal cell carcinoma

FSCN1 predicts survival and is regulated by a PI3K‐dependent mechanism in renal cell carcinoma

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