ArticleCellular oncology (Dordrecht, Netherlands)2013
Restoration of klotho expression induces apoptosis and autophagy in hepatocellular carcinoma cells.
Article in Cellular oncology (Dordrecht, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Klotho increases antioxidant defenses in astrocytes and ubiquitin-proteasome activity in neurons.Scientific reports · 2023Article
- Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer.Molecular and clinical oncology · 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
- Klotho Ameliorates Vascular Calcification via Promoting Autophagy.Oxidative medicine and cellular longevity · 2022Article
- Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease.Pharmaceutics · 2021Review
- 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
- Clinicopathological and Prognostic Significance of Klotho and Estrogen Receptors Expression in Human Hepatocellular Carcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Article
- Klotho as Potential Autophagy Regulator and Therapeutic Target.Frontiers in pharmacology · 2021Review
- Sphingomyelinases and Liver Diseases.Biomolecules · 2020Review
- Klotho Exerts an Emerging Role in Cytokinesis.Genes · 2020Article
- Klotho (rs1207568 and rs564481) gene variants and colorectal cancer risk.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2020Article
- Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer.Frontiers in cell and developmental biology · 2020Review
- Dietary phosphate restriction attenuates polycystic kidney disease in mice.American journal of physiology. Renal physiology · 2020Article
- The Involvement of NF-κB/Klotho Signaling in Colorectal Cancer Cell Survival and Invasion.Pathology oncology research : POR · 2019Article
- DNA methylation-mediated Klotho silencing is an independent prognostic biomarker of head and neck squamous carcinoma.Cancer management and research · 2019Article
- Article
- α-Klotho Expression in Mouse Tissues Following Acute Exhaustive Exercise.Frontiers in physiology · 2019Article
- Changes in expression of klotho affect physiological processes, diseases, and cancer.Iranian journal of basic medical sciences · 2018Review
- Klotho ameliorates sepsis-induced acute kidney injury but is irrelevant to autophagy.OncoTargets and therapy · 2018Article
- Necrostatin-1 Attenuates Cisplatin-Induced Nephrotoxicity Through Suppression of Apoptosis and Oxidative Stress and Retains Klotho Expression.Frontiers in pharmacology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeKlotho has been identified as a tumor suppressor in several human malignancies including hepatocellular carcinoma (HCC). However, the signaling pathways involved in the tumor suppressive role of klotho in HCC have not been reported. Here, we investigated the role of klotho in HCC cell proliferation, apoptosis, autophagy, and invasion, as well as its associated signal transduction pathways.
methodsRestoration of klotho gene expression was established by delivering a klotho gene expression vector into the human HCC cell lines HepG2 and MHCC-97-H. Cell viability was measured using a cell counting (CCK-8) assay and apoptosis was analyzed through flow cytometry. Autophagy was measured via LC3-I and LC3-II protein expression levels and tumor cell invasion was assessed using a Matrigel invasion chamber assay. Expression and phosphorylation of several apoptosis and survival related proteins were assessed using Western blot assays.
resultsExogenous klotho gene expression significantly inhibited HCC cell proliferation, induced HCC cell apoptosis, increased LC3-I and LC3-II protein expression in HCC cells, and decreased migration of HCC cells in a Matrigel invasion chamber assay. Exogenous klotho gene expression also down-regulated the phosphorylation levels of the IGF-1 receptor, and the downstream Akt, ERK, and p70S6K proteins. Both apoptosis and autophagy inhibitors decreased klotho-induced apoptosis and autophagy.
conclusionKlotho is a tumor suppressor that, through the regulation of IGF-1R phosphorylation and subsequent activation of downstream Akt-p70S6K and ERK signaling, regulates HCC tumor cell proliferation, apoptosis, autophagy and invasion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.