SPOP promotes tumor progression via activation of β-catenin/TCF4 complex in clear cell renal cell carcinoma.

SPOP promotes tumor progression via activation of β-catenin/TCF4 complex in clear cell renal cell carcinoma. Int J Oncol. 2016 Sep;49(3):1001-8 Authors: Zhao W, Zhou J, Deng Z, Gao Y, Cheng Y Abstract Renal cell carcinoma (RCC) is the most common type of kidney cancer, about one third of the cases are diagnosed at advanced stages with metastases and effective treatments for metastatic RCC are lacking. The molecular events supporting RCC progression remain poorly understood. SPOP, an E3 ubiquitin ligase component, was recently showed to sufficiently promote RCC tumorigenesis, however, other potential functions of SPOP in RCC have not been studied. In the present investigation, by assessing the immunohistochemical staining of SPOP in urological tumors, we found the protein was highly expressed in RCC, in particular, it was specifically expressed in clear cell RCC. cDNA microarray data showed that SPOP mRNA level was significantly increased in clear cell RCC compared to normal kidney tissues, which might be the result of the abnormal DNA copy number of this gene. More interestingly, SPOP was positive in tumors with local invasion or metastasis, and it was associated with tumor recurrence-free survival of clear cell RCC patients. Further in vitro assays demonstrated that SPOP drove RCC epithelial-mesenchymal transition (EMT) and promoted cell invasion. Mechanistically, SPOP enhanced β-catenin protein expression as well as its nuclear t...
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research