The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome

  • Kim, Ji-Hee (Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine) ;
  • Hwang, Kyu-Hee (Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine) ;
  • Lkhagvadorj, Sayamaa (Department of Pathology, Yonsei University Wonju College of Medicine) ;
  • Jung, Jae Hung (Department of Urology, Yonsei University Wonju College of Medicine) ;
  • Chung, Hyun Chul (Department of Urology, Yonsei University Wonju College of Medicine) ;
  • Park, Kyu-Sang (Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine) ;
  • Kong, In Deok (Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine) ;
  • Eom, Minseob (Department of Pathology, Yonsei University Wonju College of Medicine) ;
  • Cha, Seung-Kuy (Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine)
  • Received : 2016.02.22
  • Accepted : 2016.03.10
  • Published : 2016.05.01
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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.

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References

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