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Updated: Mar 21, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome
Ji-Hee Kim1, Kyu-Hee Hwang1, Sayamaa Lkhagvadorj2
1Department of Physiology and Global Medical Science, Yonsei University Wonju College of Medicine, Wonju 26426, Korea.
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.
Insights
Klotho acts as a tumor suppressor in clear cell renal cell carcinoma (ccRCC). It inhibits growth factor signaling, suggesting Klotho as a potential therapeutic agent for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Klotho is a tumor suppressor in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC).
- Altered growth factor receptor signaling is implicated in ccRCC development.
- The specific role of Klotho in ccRCC and its interaction with insulin-like growth factor-1 receptor (IGF-1R) signaling are not well understood.
Purpose of the Study:
- To investigate the role of Klotho in ccRCC.
- To determine the clinical relevance of Klotho expression in ccRCC.
- To elucidate the mechanism by which Klotho suppresses ccRCC through IGF-1R signaling.
Main Methods:
- Analysis of Klotho and IGF-1R expression levels in ccRCC tumor tissues versus adjacent non-neoplastic parenchyma.
- Correlation of Klotho expression with ccRCC grade and clinical outcomes.
- Investigation of Klotho's effect on IGF-1-stimulated cell proliferation and migration, including PI3K/Akt pathway inhibition.
Main Results:
- Klotho expression was lower, and IGF-1R expression was higher in ccRCC tumor tissues compared to normal tissues.
- Low Klotho expression correlated with higher ccRCC grade and poorer clinical outcomes.
- Klotho suppressed IGF-1-induced proliferation and migration by inhibiting the PI3K/Akt pathway.
Conclusions:
- Klotho acts as a tumor suppressor in ccRCC by inhibiting IGF-1R signaling.
- Klotho expression is a favorable prognostic factor for ccRCC.
- Klotho represents a potential therapeutic target or agent for ccRCC treatment.
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