scholarly journals Downregulation of SNX5 By KLF9 Leads to Clear Cell Renal Cell Carcinoma Progression By Inducing CD44 Internalization and Suppressing Epithelial-to-Mesenchymal Transition

2021 ◽  
Author(s):  
Qingqing Zhou ◽  
Jiajun Li ◽  
Chao Ge ◽  
Jinsi Chen ◽  
Wei Tian ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Background: Aberrant expression of SNX5 can contribute to tumourigenesis, invasion, and metastasis of several human cancers. However, the clinicopathological and biological significance of SNX5 in clear cell renal cell carcinoma (ccRCC) remain unclear. The aim of this study was to examine the role of SNX5 in the progression of ccRCC.Methods: Immunohistochemical (IHC), Western blot, qRT-PCR, western blot, flow cytometry and immunofluorescence were used to detect the expression of indicated molecules. The biological role of SNX5 in ccRCC cells was evaluated by CCK8, colony formation, transwell assay, subcutaneous tumor formation as well as veil tail injection. ChIP assay and luciferase reporter assay were used to determine the direct binding of KLF9 to the promoter of the SNX5 gene.Results: SNX5 expression was downregulated in human ccRCC tissues. SNX5 expression was negatively correlated with tumor size, AJCC stage, tumor thrombus of inferior vena cava (IVC) and poor prognosis of ccRCC. Ectopic expression of SNX5 inhibited ccRCC cell proliferation and metastasis whereas knockdown of SNX5 increase these activities both in vitro and in vivo. Mechanistically, overexpression of SNX5 blocked internalization and intracellular trafficking of CD44 in ccRCC cells. Exogenous expression of CD44 partially rescued the inhibitory effects of SNX5 on the proliferation and invasion activity of ccRCC cells. Knockdown of SNX5 in ccRCC cells was associated with epithelial mesenchymal transition (EMT), including the down-regulation of E-cadherin, ZO-1 and Claudin-1 and the concomitant up-regulation of Snail and N-cadherin. In addition, SNX5 inhibited TGF-β-induced migration, invasion and EMT in ccRCC cells. Moreover, we observed a significant correlation between SNX5 expression and E-cadherin levels in ccRCC patients. In addition, KLF9 directly bound to the SNX5 promoter and increased SNX5 transcription. SNX5 expression was closely correlated with KLF9 expression in ccRCC. Moreover, we found that the combination of SNX5 and CD44 or E-cadherin or KLF9 was a more powerful predictor of poor prognosis than either parameter alone.Conclusion: Collectively, our data reveal a mechanism that KLF9-mediated SNX5 expression was associated with poor prognosis via trafficking of CD44 and promoting EMT in ccRCC. SNX5 may be a potential prognostic biomarker and therapeutic target for patients with ccRCC.

scholarly journals FGL1 as a Novel Mediator and Biomarker of Malignant Progression in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zheng Lv ◽  
Bo Cui ◽  
Xing Huang ◽  
Hua-Yi Feng ◽  
Tao Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
T Cell Activation ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Cell Activation ◽  
Epithelial To Mesenchymal Transition ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Mesenchymal Transition

Clear cell renal cell carcinoma (ccRCC), which is the most prevalent renal cell carcinoma subtype, has a poor prognosis. Emerging strategies for enhancing the immune response in ccRCC therapy are currently being investigated. Fibrinogen-like Protein 1(FGL1) is a novel mechanism that tumors may use to evade the immune system by binding LAG-3 and negatively regulating T cells. In this study, we aimed at investigating the underlying mechanism of FGL1 in ccRCC, and its expression and prognostic value. We found that FGL1 was upregulated in tumor tissues and plasma specimens of ccRCC patients. High FGL1 expression predicted a poor prognosis for ccRCC patients. We also discovered that overexpression of FGL1 enhances RCC cell migration, invasion, and metastasis by activating the epithelial-to-mesenchymal transition (EMT). Consistent with these results, we identified a significant positive correlation between expression of FGL1 and EMT-related genes through tissue microarray analysis. Gene-expression analysis revealed that FGL1-deficient ccRCC cell lines had altered transcriptional output in inflammatory response, cell-cell signaling, negative regulation of T cell activation, and intracellular signal transduction. Depletion of FGL1 significantly inhibited tumor growth and lung metastasis in orthotopic xenograft mouse model. Infiltration of myeloid-derived CD11b+ and Ly6G+ immune cells in tumor microenvironment (TME) was strikingly decreased when FGL1 expression reduced. Therefore, increased FGL1 expression in ccRCC is positively correlated with poor prognosis. Mechanistically, FGL1 facilitates the EMT process and modulates TME, which promotes ccRCC progression and metastasis. Consequently, targeting FGL1 can potentially improve clinical outcome of ccRCC patients.

scholarly journals Pancreatic ductal adenocarcinoma concomitant with pancreatic metastases of clear-cell renal cell carcinoma: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Lena Haeberle ◽  
Melanie Busch ◽  
Julian Kirchner ◽  
Georg Fluegen ◽  
Gerald Antoch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Ductal Adenocarcinoma ◽  
Special Role ◽  
Cell Renal Cell Carcinoma ◽  
Pancreatic Metastases

Abstract Background Metastatic spread to the pancreas is a rare event. Renal cell carcinoma represents one possible site of origin of pancreatic metastases. Renal cell carcinoma often metastasizes late and exclusively to the pancreas, suggesting a special role of renal cell carcinoma among primaries metastasizing to the pancreas. Even rarer, renal cell carcinoma may occur simultaneously with pancreatic ductal adenocarcinoma. Case presentation We present the case of a 78-year-old male Caucasian patient with a history of clear-cell renal cell carcinoma treated with oncological left nephrectomy 20 years before. The patient was diagnosed with pancreatic ductal adenocarcinoma by fine-needle aspiration cytology. At our institution, he received neoadjuvant therapy with folic acid, fluorouracil, irinotecan, oxaliplatin for borderline-resectable pancreatic ductal adenocarcinoma, and subsequently underwent total pancreatectomy. Upon resection, pancreatic ductal adenocarcinoma as well as two metachronous metastases of clear-cell renal cell carcinoma occurring simultaneously and cospatially with pancreatic ductal adenocarcinoma were diagnosed in the pancreatic body. Conclusions Renal cell carcinoma metastases of the pancreas are rare and often occur decades after the initial diagnosis of renal cell carcinoma. The combination of renal cell carcinoma metastases and pancreatic ductal adenocarcinoma is even rarer. However, the possibility should be considered by clinicians, radiologists, and pathologists. The special role of renal cell carcinoma as a site of origin of pancreatic metastasis should be further elucidated.

scholarly journals The Oncogenic Role of COL23A1 in Clear Cell Renal Cell Carcinoma

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Fujiang Xu ◽  
Kun Chang ◽  
Jian Ma ◽  
Yuanyuan Qu ◽  
Huyang Xie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

scholarly journals Increased expression of MUC3A is associated with poor prognosis in localized clear-cell renal cell carcinoma

Oncotarget ◽  
2016 ◽  
Vol 7 (31) ◽  
pp. 50017-50026 ◽  
Author(s):  
Tian Niu ◽  
Yidong Liu ◽  
Yuan Zhang ◽  
Qiang Fu ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Investigation of the Role of microRNA Associated with the VHL-HIFα-Dependent Pathway in Patients with Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 56 (3) ◽  
pp. 363-369
Author(s):  
E. A. Klimentova ◽  
I. R. Gilyazova ◽  
M. A. Bermisheva ◽  
A. M. Blinnikova ◽  
R. I. Safiullin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Dependent Pathway
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