title: Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome.
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.
authors.affiliation: Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Kyu-Hee
authors.initials: KH
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Sayamaa
authors.initials: S
authors.lastname: Lkhagvadorj
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Jae Hung
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.; Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Park
authors.affiliation: Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.; Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: In Deok
authors.initials: ID
authors.lastname: Kong
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Minseob
authors.initials: M
authors.lastname: Eom
authors.affiliation: Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.; Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
authors.forename: Seung-Kuy
authors.initials: SK
authors.lastname: Cha
keywords: Clear cell renal cell carcinoma; IGF-1 receptor; Klotho; Migration; Prognosis