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

Oncol Rep. 2017 Sep;38(3):1551-1560. doi: 10.3892/or.2017.5789. Epub 2017 Jul 4.

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 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.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • Humans
  • Immunohistochemistry / methods
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / genetics*
  • Wnt Signaling Pathway / genetics*

Substances

  • FERMT3 protein, human
  • Membrane Proteins
  • Neoplasm Proteins