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 PI3K/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. This article is protected by copyright. All rights reserved.
Journal of cellular physiology. 2017 Nov 17 [Epub ahead of print]
Mengping Zhang, Zhijian Zhao, Xiaolu Duan, Ping Chen, Zhenwei Peng, Huijuan Qiu
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China., Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Department of VIP, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.