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

Abstract

Kindlin-2 is an integrin-interacting, FERMdomain 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.

Prognosis of clear cell renal cell carcinoma (ccRCC) based on a six-lncRNA-based risk score: an investigation based on RNA-sequencing data

“…VEGFA was also reported to act as a stimulus of ccRCC cell migration, invasion, and angiogenesis [48]. Thus, these six novel lncRNAs may begin their function by activating genes in the ‘Renal cell carcinoma pathway.’ In addition to the ‘Renal cell carcinoma pathway,’ by modulating the ‘Wnt signaling pathway,’ the lncRNAs CCAT2 and Kindlin‑2 appear to promote clear cell renal cell carcinoma progression [50, 51]. We also found that the top three KEGG pathways for DEGs of patients in the high-risk group included KEGG_PRIMARY_IMMUNODEFICIENCY, KEGG_OLFACTORY_TRANSDUCTION, and KEGG_ALLOGRAFT_REJECTION, while in the low-risk group the three most dominant pathways were KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS, KEGG_OXIDATIVE_PHOSPHORYLATION, and KEGG_PEROXISOME.…”

Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status

“…A nucleolar protein MSP58 positively regulated the proliferation and invasion of ccRCC through the Wnt/β-catenin axis [76]. Kindlin-2, known as an integrin-interacting and FERM-domain containing protein, involved in the ccRCC progression through the Wnt pathway [77]. RNA binding protein QK1, through Wnt and GPCR pathway, inhibits the ccRCC proliferation by attuned cell contact inhibition [78].…”