Korean J Physiol Pharmacol.  2016 May;20(3):297-304. 10.4196/kjpp.2016.20.3.297.

Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome

Affiliations
  • 1Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea. skcha@yonsei.ac.kr
  • 2Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea. eomm@yonsei.ac.kr
  • 3Department of Urology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
  • 4Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.

Abstract

Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.

Keyword

Clear cell renal cell carcinoma; IGF-1 receptor; Klotho; Migration; Prognosis
Full Text Links
  • KJPP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2021 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr