Abstract
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 invitro, whereas knockdown of Kindlin‑2 inhibited cell migration and invasion. Knockdown of Kindlin‑2 also inhibits ACHN cell proliferation invitro and tumorigenesis invivo. 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.
Highlights
Renal cell carcinoma (RCC) is the most common kidney cancer, and has become the 7th most common cancer in men in the USA
Expression of Kindlin‐2 correlates with higher tumor grade, lymph node metastasis and poor prognosis in clear cell RCC (CCRCC) patients
These results indicate the involvement of Kindlin‐2 in the process of CCRCC progression
Summary
Renal cell carcinoma (RCC) is the most common kidney cancer, and has become the 7th most common cancer in men in the USA. Despite advances in early detection of RCC, ~20-30% of patients still present with metastatic disease at diagnosis, and around one third of patients undergoing nephrectomy for localized tumor eventually develop metastases. Patients with localized RCC tend to have a better prognosis. The prognosis for metastatic RCC remains poor, and the 5-year survival rate is
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