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- Title
Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.
- Authors
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
- 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.
- Subjects
RENAL cell carcinoma; INSULIN receptors; TUMORS; PROGNOSIS; TUMOR suppressor genes
- Publication
Korean Journal of Physiology & Pharmacology, 2016, Vol 20, Issue 3, p297
- ISSN
1226-4512
- Publication type
Article
- DOI
10.4196/kjpp.2016.20.3.297