ArticleJournal of experimental & clinical cancer research : CR2010
Klotho inhibits growth and promotes apoptosis in human lung cancer cell line A549.
Article in Journal of experimental & clinical cancer research : CR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 109 citations in OpenAlex.
- Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026Review
- The Role of Klotho in Oral and Maxillofacial Diseases: Mechanisms and Research Progress.Biomolecules · 2025Review
- Association ofInternational journal of molecular sciences · 2025Article
- The inflection point: α-Klotho levels and the risk of all-cause mortality.Frontiers in endocrinology · 2025Article
- Analysis of the correlation between serum Klotho and FeNO: a cross-sectional study from NHANES (2007-2012).BMC pulmonary medicine · 2024Article
- Protein interaction networks characterizing the A549 cells Klotho transfected are associated with activated pro-apoptotic Bim and suppressed Wnt/β-catenin signaling pathway.Scientific reports · 2024Article
- Association Between Serum Klotho and Chronic Obstructive Pulmonary Disease in US Middle-Aged and Older Individuals: A Cross-Sectional Study from NHANES 2013-2016.International journal of chronic obstructive pulmonary disease · 2024Article
- Advances in genetic profile and therapeutic strategy of pulmonary large cell neuroendocrine carcinoma.Frontiers in medicine · 2024Review
- [Research Progress of Klotho in Lung Neoplasms].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- β-Klotho inhibits CSF-1 secretion and delays the development of endometrial cancer.Cell cycle (Georgetown, Tex.) · 2022Article
- Review
- Impact of cytotoxic agents or apoptosis stimulants on αklotho in MDCK, NRK-52E and HK2 kidney cells.Aging · 2022Article
- SHANK1 facilitates non-small cell lung cancer processes through modulating the ubiquitination of Klotho by interacting with MDM2.Cell death & disease · 2022Article
- Investigation of the Role of Induced Overexpression of the Isolated Secreted Klotho on the A-172 Human Glioblastoma Cells.Journal of molecular neuroscience : MN · 2022Article
- CircRNA ITCH: Insight Into Its Role and Clinical Application Prospect in Tumor and Non-Tumor Diseases.Frontiers in genetics · 2022Review
- Clinical Experience of Diagnosis and Surgical Treatment of 6 Cases of Acute Subhepatic Appendicitis.Journal of healthcare engineering · 2022Article
- A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy.Cancers · 2021Article
- 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
- Zika virus dysregulates the expression of astrocytic genes involved in neurodevelopment.PLoS neglected tropical diseases · 2021Article
- Genetic Liability to Insomnia and Lung Cancer Risk: A Mendelian Randomization Analysis.Frontiers in genetics · 2021Article
2 more citing papers are in PubMed but not listed here.
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4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundKlotho, as a new anti-aging gene, can shed into circulation and act as a multi-functional humoral factor that influences multiple biological processes. Recently, published studies suggest that klotho can also serve as a potential tumor suppressor. The aim of this study is to investigate the effects and possible mechanisms of action of klotho in human lung cancer cell line A549.
methodsIn this study, plasmids encoding klotho or klotho specific shRNAs were constructed to overexpress or knockdown klotho in vitro. A549 cells were respectively treated with pCMV6-MYC-KL or klotho specific shRNAs. The MTT assay was used to evaluate the cytotoxic effects of klotho and flow cytometry was utilized to observe and detect the apoptosis of A549 cells induced by klotho. The activation of IGF-1/insulin signal pathways in A549 cells treated by pCMV6-MYC-KL or shRNAs were evaluated by western blotting. The expression levels of bcl-2 and bax transcripts were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
resultsOverexpression of klotho reduced the proliferation of lung cancer A549 cells, whereas klotho silencing in A549 cells enhanced proliferation. Klotho did not show any effects on HEK-293 cells. Klotho overexpression in A549 cells was associated with reduced IGF-1/insulin-induced phosphorylation of IGF-1R (IGF-1 receptor)/IR (insulin receptor) (P < 0.01). Overexpression of klotho can promote the apoptosis of A549 cells (P < 0.01). Overexpression of klotho, a bcl family gene bax, was found up-regulated and bcl-2, an anti-apoptosis gene, was found down-regulated (P < 0.01). In contrast, bax and bcl-2 were found down-regulated (P < 0.05) and up-regulated (P < 0.01), respectively when silencing klotho using shRNAs.
conclusionsKlotho can inhibit proliferation and increase apoptosis of A549 cells, this may be partly due to the inhibition of IGF-1/insulin pathways and involving regulating the expression of the apoptosis-related genes bax/bcl-2. Thus, klotho can serve as a potential tumor suppressor in A549 cells.
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