Downregulation of FOXO3a Promotes Tumor Metastasis and Is Associated with Metastasis-Free Survival of Patients with Clear Cell Renal Cell Carcinoma

• DOI: 10.1158/1078-0432.ccr-13-1687
• Publication Date: 2014-02-01T04:57:37Z
• Authors: Dong Ni; Xin Ma; Hong-Zhao Li; Yu Gao; Xin-Tao Li; Yu Zhang; Qing Ai; Peng Zhang; Er-Lin Song; Qing-Bo Huang; Yang Fan; Xu Zhang
• Keywords: Primary tumor

To explore the mechanisms underlying clear-cell renal cell carcinoma (ccRCC) metastasis using transcriptional profiling and bioinformatics analysis of ccRCC samples, to elucidate role FOXO3a in metastasis.Gene expression was performed four primary metastatic five nonmetastatic samples. The mRNA protein levels samples were investigated by real-time reverse transcription PCR immunohistochemistry, respectively. association between metastasis-free survival patients with analyzed. Biologic functions cancer lines investigated. influence on tumor also studied vivo orthotopic xenograft model. Finally, mechanism which attenuation could increase invasion migration cells explored.Bioinformatics data identified as a key factor metastasis. decreased Patients low had poor (P = 0.003). Knocking down induced cells. Induced overexpression SN12-PM6 inhibit vivo. Downregulation increased SNAIL1 expression, thereby activating epithelial-mesenchymal transition (EMT) RCC lines.The loss EMT upregulating SNAIL1, promoted vitro Thus, be considered an independent prognostic marker occult metastases.