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KMID : 0811720160200030297
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Korean Journal of Physiology & Pharmacology
2016 Volume.20 No. 3 p.297 ~ p.304
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Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome
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Kim Ji-Hee
Hwang Kyu-Hee
Sayamaa Lkhagvadorj
Jung Jae-Hung
Chung Hyun-Chul
Park Kyu-Sang
Kong In-Deok
Eom Min-Seob
Cha Seung-Kuy
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Abstract
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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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KEYWORD
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Clear cell renal cell carcinoma, IGF-1 receptor, Klotho, Migration, Prognosis
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