ArticleCancer cell international2013
Restoration of klotho gene expression induces apoptosis and autophagy in gastric cancer cells: tumor suppressive role of klotho in gastric cancer.
Article in Cancer cell international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
- Klotho protein: a multifaceted regulator in aging and cancer dynamics.Molecular biology reports · 2025Review
- IGF-1 Signaling Modulates Oxidative Metabolism and Stress Resistance in ARPE-19 Cells Through PKM2 Function.International journal of molecular sciences · 2024Article
- Klotho: A new therapeutic target in diabetic retinopathy?World journal of diabetes · 2023Review
- The Anti-Aging Hormone Klotho Promotes Retinal Pigment Epithelium Cell Viability and Metabolism by Activating the AMPK/PGC-1α Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Review
- Impact of cytotoxic agents or apoptosis stimulants on αklotho in MDCK, NRK-52E and HK2 kidney cells.Aging · 2022Article
- Epigenetic regulation of autophagy in coronavirus disease 2019 (COVID-19).Biochemistry and biophysics reports · 2022Article
- Molecular pathogenesis and emerging targets of gastric adenocarcinoma.Journal of surgical oncology · 2022Review
- Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer.Molecular and clinical oncology · 2022Article
- Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations.Frontiers in aging · 2022Review
- A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy.Cancers · 2021Article
- Epigenetic regulation of autophagy: A key modification in cancer cells and cancer stem cells.World journal of stem cells · 2021Review
- Recent advances of SIRT1 and implications in chemotherapeutics resistance in cancer.American journal of cancer research · 2021Review
- Klotho as Potential Autophagy Regulator and Therapeutic Target.Frontiers in pharmacology · 2021Review
- Klotho (rs1207568 and rs564481) gene variants and colorectal cancer risk.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2020Article
- Klotho and the Treatment of Human Malignancies.Cancers · 2020Review
- Klotho rewires cellular metabolism of breast cancer cells through alteration of calcium shuttling and mitochondrial activity.Oncogene · 2020Article
- Transcriptional regulation of autophagy-lysosomal pathway in cancer.Thoracic cancer · 2020Review
- 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
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe loss of tumor suppressor gene expression is involved in the carcinogenesis of gastric cancer (GC). Klotho is a recently identified tumor suppressor gene that epigenetically inactivated in gastric cancer. However, the signaling pathways involved in the suppressive role of klotho have rarely been reported in gastric cancer. In this study, we investigated the involvement of klotho in gastric cancer cell proliferation, apoptosis, and autophagy as well as the associated signaling.
methodsMethylation of klotho gene promoter in GC-7901, MNK-45 and AGS gastric cancer cells as well as GES-1 normal gastric epithelial cells was detected by bisulfate-based PCR. Restoration of klotho gene expression was established by applying a demethylating agent and delivering aklotho gene expression vector into GC-7901 cells. Cell viability was measured by CCK-8 assay. Cell apoptosis and cycling were analyzed by flow cytometry. Autophagy was measured by detecting LC3-I and LC3-II expression. Protein levels and phosphorylation were measured by Western blot assay.
resultsMethylation of klotho gene promoter and expression of the klotho gene were detected in GC cells. Restoration of klotho gene expression significantly inhibited cell proliferation, induced cell apoptosis, and increased LC3-I/LC3-II expression in GC cells. Restoration of klotho gene expression downregulated the phosphorylation levels of IGF-1 receptor, IRS-1, PI3K, Akt, and mTOR proteins. Both apoptosis and autophagy inhibitors blocked klotho-induced apoptosis and autophagy.
conclusionKlotho is a tumor suppressor in gastric cancer, which regulates IGF-1R phosphorylation and the subsequent activation of IRS-1/PI3K/Akt/mTOR signaling, tumor cell proliferation, apoptosis, and autophagy.
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Registered trials
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.