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

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.