Abstract
δ‐Catenin is a unique member of the catenin family and is proved to be overexpressed in diverse human cancer types. However, the clinical significance and underling mechanism of δ‐catenin expression in renal cell carcinoma (RCC) remain elusive. Herein, we detected the protein expression of δ‐catenin in 28 clinical specimens of paired renal cancer tissues and normal renal tissues by Western blot analysis. δ‐Catenin expression in 58 cases of renal cell carcinoma was also examined by immunohistochemistry, and its association with clinicopathological factors was analyzed by statistical analysis. In vitro and in vivo assays were employed to further explore the biological role of δ‐catenin in RCC. The results showed that δ‐catenin was highly expressed in both clinical samples and cell lines of RCC. RCC patients with higher δ‐catenin expression had a more advanced pTNM stage and tumor stage as well as lymph nodes metastasis than those with lower expression. By regulating the nuclear translocation of β‐catenin and β‐catenin‐mediated oncogenic signals, δ‐catenin promoted proliferation and inhibited apoptosis in RCC. In vivo assay indicated δ‐catenin facilitated tumor growth in ACHN cell xenograft mouse model. Taken together, our study suggests that δ‐catenin might be considered as a novel prognostic indicator and actionable target for gene therapy in renal cell carcinoma.
Highlights
Renal cell carcinoma (RCC) is the ninth most common malignancy, with 403 262 new cases diagnosed and 175 098 cancer deaths worldwide in 2018.1,2 In the management of localized or locally advanced RCC, surgical resection including partial and radical nephrectomy is a common treatment strategy.[3,4] up to 40% risk of developing recurrence after nephrectomy.[4,5] For patients with metastatic RCC, cytoreductive nephrectomy followed by systemic drugs is an established treatment approach.[6,7] the disease still progresses after therapy and metastasis is the major cause of their death.[1]
It has been proven that δ-catenin has ectopic overexpression in lung cancer and prostate cancer and promotes tumor progression,[12-14] but little is known about its biological role and the associated signaling pathways in RCC
Based on the results of Western blot and immunohistochemistry, we found that the level of δ-catenin is elevated in clinical tissue samples with RCC
Summary
Renal cell carcinoma (RCC) is the ninth most common malignancy, with 403 262 new cases diagnosed and 175 098 cancer deaths worldwide in 2018.1,2 In the management of localized or locally advanced RCC, surgical resection including partial and radical nephrectomy is a common treatment strategy.[3,4] up to 40% risk of developing recurrence after nephrectomy.[4,5] For patients with metastatic RCC, cytoreductive nephrectomy followed by systemic drugs is an established treatment approach.[6,7] the disease still progresses after therapy and metastasis is the major cause of their death.[1]. The precise role of δ-catenin in tumorigenesis and development of RCC is still poorly understood, neither is the correlation between its expression and clinical pathological parameters. Our results illuminated that elevated δ-catenin expression in RCC caused the activation of β-catenin and its target genes, thereby affecting proliferation and apoptosis.
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