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Updated: Oct 6, 2025
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
SNX5 suppresses clear cell renal cell carcinoma progression by inducing CD44 internalization and
Qingqing Zhou1, Jiajun Li1, Chao Ge1
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Aberrant expression of SNX5 can contribute to tumorigenesis, invasion, and metastasis of several human cancers. However, the clinicopathological and biological significance of SNX5 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, we found that SNX5 expression was downregulated and negatively correlated with tumor size, American Joint Committee on Cancer stage, tumor thrombus of inferior vena cava, and poor prognosis in human ccRCC. Ectopic expression of SNX5 inhibited ccRCC cell proliferation and metastasis, whereas knockdown of SNX5 increased these activities both in vitro and in vivo. Mechanistically, overexpression of SNX5 blocked internalization and intracellular trafficking of CD44 in ccRCC cells. Knockdown of SNX5 was associated with epithelial-to-mesenchymal transition (EMT) in ccRCC cells. Overexpression of SNX5 inhibited TGF-β-induced migration, invasion, and EMT in ccRCC cells. KLF9 directly bound to the SNX5 promoter and increased SNX5 transcription. 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. 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.
Insights
Downregulated SNX5 expression in clear cell renal cell carcinoma (ccRCC) correlates with poor prognosis. SNX5 inhibits ccRCC cell proliferation and metastasis by affecting CD44 trafficking and epithelial-mesenchymal transition (EMT).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant SNX5 expression is linked to tumorigenesis and metastasis in various cancers.
- The role of SNX5 in clear cell renal cell carcinoma (ccRCC) pathogenesis is not well understood.
Purpose of the Study:
- To investigate the clinicopathological and biological significance of SNX5 in ccRCC.
- To elucidate the underlying mechanisms of SNX5's function in ccRCC progression.
Main Methods:
- Analysis of SNX5 expression in ccRCC tissues and correlation with clinicopathological features.
- In vitro and in vivo experiments assessing the effects of SNX5 overexpression and knockdown on ccRCC cell behavior.
- Investigation of SNX5's role in CD44 trafficking, epithelial-to-mesenchymal transition (EMT), and TGF-β signaling.
- Identification of transcription factors regulating SNX5 expression.
Main Results:
- SNX5 expression was downregulated in ccRCC and inversely correlated with tumor size, AJCC stage, and inferior vena cava tumor thrombus.
- SNX5 overexpression suppressed ccRCC cell proliferation and metastasis, while SNX5 knockdown enhanced these processes.
- SNX5 inhibited CD44 internalization and intracellular trafficking, suppressed EMT, and blocked TGF-β-induced migration and invasion.
- KLF9 directly regulated SNX5 transcription.
- Combined SNX5, CD44, E-cadherin, or KLF9 levels were potent predictors of poor prognosis.
Conclusions:
- KLF9-mediated SNX5 expression is associated with poor ccRCC prognosis through CD44 trafficking and EMT promotion.
- SNX5 serves as a potential prognostic biomarker and therapeutic target for ccRCC patients.
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