ArticleCancer science2013
Klotho suppresses tumor progression via inhibiting PI3K/Akt/GSK3β/Snail signaling in renal cell carcinoma.
Article in Cancer science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Klotho antiaging protein: molecular mechanisms and therapeutic potential in diseases.Molecular biomedicine · 2025Review
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- Co-regulatory mechanisms and potential markers of oxidative stress-related genes in vitiligo and alopecia areata.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2024Article
- Klotho in Cancer: Potential Diagnostic and Prognostic Applications.Diagnostics (Basel, Switzerland) · 2023Review
- KL is a favorable prognostic factor related immune for clear cell renal cell carcinoma.European journal of medical research · 2023Article
- [Research Progress of Klotho in Lung Neoplasms].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Article
- β-Klotho Promotes the Development of Intrauterine Adhesions via the PI3K/AKT Signaling Pathway.International journal of molecular sciences · 2022Article
- Review
- Establishing a prognostic model of ferroptosis- and immune-related signatures in kidney cancer: A study based on TCGA and ICGC databases.Frontiers in oncology · 2022Article
- Enhancement of Apo2L/TRAIL signaling pathway receptors by the activation of Klotho gene with CRISPR/Cas9 in Caco-2 colon cancer cells.Medical oncology (Northwood, London, England) · 2021Article
- Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating KlothoFrontiers in oncology · 2021Article
- Cyclovirobuxine inhibits the progression of clear cell renal cell carcinoma by suppressing the IGFBP3-AKT/STAT3/MAPK-Snail signalling pathway.International journal of biological sciences · 2021Article
- MicroRNA-203 inhibits epithelial-mesenchymal transition, migration, and invasion of renal cell carcinoma cells via the inactivation of the PI3K/AKT signaling pathway by inhibiting CAV1.Cell adhesion & migration · 2020Article
- Klotho and the Treatment of Human Malignancies.Cancers · 2020Review
- γ-Klotho is correlated with resistance to docetaxel in castration-resistant prostate cancer.Oncology letters · 2020Article
- Dietary phosphate restriction attenuates polycystic kidney disease in mice.American journal of physiology. Renal physiology · 2020Article
- Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer.Frontiers in cell and developmental biology · 2020Review
- Rab8 GTPase regulates Klotho-mediated inhibition of cell growth and progression by directly modulating its surface expression in human non-small cell lung cancer.EBioMedicine · 2019Article
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klotho is an anti-aging protein predominantly expressed in renal tubular epithelial cells. Although Klotho was recently identified as a tumor suppressor gene in a variety of cancers, the potential role and molecular events for Klotho in renal cell carcinoma (RCC) remain obscure. In the present study, immunohistochemical staining in tissue microarrays containing 125 RCC samples showed that intratumoral Klotho levels were negatively correlated with tumor size, TNM stage and nuclear grade. The overall survival rate of RCC patients with high Klotho expression was significantly higher than that of patients with low Klotho expression. Functional analysis after gain and loss of Klotho expression revealed that Klotho blunted epithelial-mesenchymal transition and cellular migration and invasion in RCC. Also, no alteration of α-2,6-sialidase activity was found after Klotho overexpression in RCC. The molecular signals for this phenomenon involved the Klotho-mediated inhibition of PI3K/Akt/GSK3β/Snail pathway. Importantly, compared to localized RCC tissues, advanced RCC tissues exhibited low Klotho expression accompanied with high pAkt and Snail expression. These results indicate Klotho acts as a tumor suppressor by inhibiting PI3K/Akt/GSK3β/Snail signaling, thus suppressing epithelial-mesenchymal transition and tumor migration and invasion during RCC progression. As a result, Klotho might be used as a potential therapy for advanced RCC.
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