Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.
10.4196/kjpp.2016.20.3.297
- Author:
Ji Hee KIM
1
;
Kyu Hee HWANG
;
Sayamaa LKHAGVADORJ
;
Jae Hung JUNG
;
Hyun Chul CHUNG
;
Kyu Sang PARK
;
In Deok KONG
;
Minseob EOM
;
Seung Kuy CHA
Author Information
1. Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea. skcha@yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Clear cell renal cell carcinoma;
IGF-1 receptor;
Klotho;
Migration;
Prognosis
- MeSH:
Carcinoma, Renal Cell*;
Cell Proliferation;
Prognosis;
Receptor, IGF Type 1
- From:The Korean Journal of Physiology and Pharmacology
2016;20(3):297-304
- CountryRepublic of Korea
- Language:English
-
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.
