Kindlin-2 promotes clear cell renal cell carcinoma progression through the Wnt signaling pathway

Kindlin-2 is an integrin-interacting, FERM-domain containing protein, which plays a critical role in tumor progression. However, the specific role of Kindlin-2 in renal cell carcinoma (RCC) progression has not been described. In this study we investigated the role of Kindlin-2 in progression of clear cell RCC (CCRCC), which is the most common RCC subtype, and its underlying mechanisms. Immunohistochemistry studies show that expression of Kindlin-2 in CCRCC is positively correlated with tumor grade, and Kindlin-2 expression in advanced CCRCC with lymph node metastasis was greater than in localized CCRCC. Kindlin-2 expression in CCRCC tumor specimens is also correlated with short patient survival, but is not an independent prognostic factor. Kindlin-2 promotes CCRCC cell migration and invasion in vitro, whereas knockdown of Kindlin-2 inhibited cell migration and invasion. Knockdown of Kindlin-2 also inhibits ACHN cell proliferation in vitro and tumorigenesis in vivo. Kindlin-2 may be required for Wnt pathway activation which underlies the mechanisms of Kindlin-2 promoting CCRCC progression. These findings demonstrate that expression of Kindlin-2 is associated with tumor grade, lymph node metastasis and poor prognosis in CCRCC patients. Kindlin-2 may regulate CCRCC progression through the Wnt signaling pathway, promoting CCRCC cell proliferation, migration and invasion.