| Literature DB >> 27780824 |
Yu Gao1,2, Hongzhao Li1,2, Xin Ma1,2, Yang Fan1,2, Dong Ni1,2, Yu Zhang1,2, Qingbo Huang1,2, Kan Liu1,2, Xintao Li1,2, Lei Wang1,2, Liangyou Gu1,2, Yuanxin Yao1,2, Qing Ai1,2, Qingshan Du1,2, Erlin Song3, Xu Zhang4,2.
Abstract
The transcription factor KLF6 has an essential role in the development and metastasis of multiple human cancers. Paradoxically, KLF6 expression was found to be attenuated in primary metastatic clear cell renal cell carcinoma (ccRCC), such that it is unclear how KLF6 affects malignant progression in this setting. In this study, we demonstrate that KLF6 attenuation in renal cells is sufficient to promote E2F1-mediated epithelial-mesenchymal transition and metastatic prowess. In a mouse xenograft model of human ccRCC, silencing KLF6 increased tumor cell proliferation and malignant character, whereas E2F1 silencing reversed these properties. These effects were corroborated in a metastatic model system, where we observed a greater number of pulmonary metastatic lesions formed by ccRCC cells where KLF6 was silenced and E2F1 enforced. Analysis of clinical specimens of ccRCC revealed that low levels of KLF6 and high levels of E2F1 correlated closely with ccRCC development. Overall, our results established the significance of activating the KLF6-E2F1 axis in aggressive ccRCC, defining a novel critical signaling mechanism that drives human ccRCC invasion and metastasis. Cancer Res; 77(2); 330-42. ©2016 AACR. ©2016 American Association for Cancer Research.Entities:
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Year: 2016 PMID： 27780824 DOI： 10.1158/0008-5472.CAN-16-0348
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701