KRT8 upregulation promotes tumor metastasis and is predictive of a poor prognosis in clear cell renal cell carcinoma

// Hai-Song Tan 1, * , Wei-Hua Jiang 2, * , Yi He 3, * , De-Sheng Wang 4, * , Zhen-Jie Wu 1 , Deng-Shuang Wu 1 , Li Gao 5 , Yi Bao 1 , Jia-Zi Shi 1 , Bing Liu 1 , Li-Jun Ma 2 and Lin-Hui Wang 1 1 Department of Urology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China 2 Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200336, China 3 Department of Urology, Jiaxing First Hospital, Zhejiang 314000, China 4 Department of Urology, Second People's Hospital of Bengbu City, Anhui 233000, China 5 Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China * These authors have contributed equally to this work Correspondence to: Lin-Hui Wang, email: wanglinhuicz@163.com Li-Jun Ma, email: lijun.ma@shtrhospital.com Bing Liu, email: 13501616398@163.com Keywords: clear cell renal cell carcinoma, metastasis, KRT8, IL-11, biomarker Received: January 17, 2017 Accepted: June 19, 2017 Published: July 12, 2017 ABSTRACT Keratin 8 (KRT8) plays an essential role in the development and metastasis of multiple human cancers. However, its role in clear cell renal cell carcinoma (ccRCC) remains unexplored. Here, we investigated the expression pattern, clinical significance, and function of KRT8 in ccRCC. KRT8 mRNA and protein levels were determined in two large cohorts using quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray (TMA) immunohistochemistry (IHC), respectively. We found that KRT8 expression was upregulated in ccRCC and vein tumor thrombi (VTTs). KRT8 overexpression in ccRCC was significantly correlated with aggressive characteristics and was predictive of a poor prognosis in ccRCC patients. Moreover, KRT8 overexpression in renal cancer cell lines promoted cell migration and invasion. In contrast, KRT8 knockdown suppressed ccRCC metastasis both in vitro and in vivo . In addition, our findings showed that KRT8 promoted ccRCC metastasis by increasing IL-11 expression, causing IL-11 autocrine induction, and triggering STAT3 signaling. Overall, this study established the significance of KRT8-IL-11 axis activation in aggressive ccRCC and defined a novel critical signaling mechanism that drives human ccRCC invasion and metastasis.