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

Ji Hee Kim, Kyu Hee Hwang, Sayamaa Lkhagvadorj, Jae Hung Jung, Hyun Chul Chung, Kyu Sang Park, In Deok Kong, Minseob Eom, Seung Kuy Cha

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalKorean Journal of Physiology and Pharmacology
Volume20
Issue number3
DOIs
Publication statusPublished - 2016 May

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

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