ArticleOncogene2019
Klotho suppresses colorectal cancer through modulation of the unfolded protein response.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- XBP1s-Orchestrated Soluble Mediators: Participants of Oxidative Stress in Renal Ischemia-Reperfusion Injury Following Donation After Circulatory Death.Mediators of inflammation · 2026Review
- Differential expression of ferroptosis markers, circadian regulators, KLOTHO, and classical tumor suppressors in colorectal cancer according to tumor stage: Influence of age, anatomical location, and correlation patterns.Histology and histopathology · 2025Article
- Effects of aging on anticancer therapy in murine cancer models.Cancer metastasis reviews · 2025Review
- The Impact of Klotho in Cancer: From Development and Progression to Therapeutic Potential.Genes · 2025Review
- NSAID use may decrease serum Klotho levels.Frontiers in endocrinology · 2025Article
- Recruitment of USP10 by GCS1 to deubiquitinate GRP78 promotes the progression of colorectal cancer via alleviating endoplasmic reticulum stress.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/βKlotho/FGFs Pathways in Mice.International journal of molecular sciences · 2023Article
- [Research Progress of Klotho in Lung Neoplasms].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.Life (Basel, Switzerland) · 2023Review
- A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation.Archivum immunologiae et therapiae experimentalis · 2023Article
- Association of serum Klotho levels with cancer and cancer mortality: Evidence from National Health and Nutrition Examination Survey.Cancer medicine · 2023Article
- Alpha-Klotho in Parkinson's disease: a perspective on experimental evidence and potential clinical implications.Neural regeneration research · 2022Article
- 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
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer.Molecular and clinical oncology · 2022Article
- A Transgenic Model Reveals the Role of Klotho in Pancreatic Cancer Development and Paves the Way for New Klotho-Based Therapy.Cancers · 2021Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klotho is an anti-aging transmembrane protein, which can be shed and function as a hormone. Accumulating data indicate klotho as a tumor suppressor in a wide array of malignancies and indicate the subdomain KL1 as the active region of the protein. We aimed to study the role of klotho as a tumor suppressor in colorectal cancer. Bioinformatics analyses of TCGA datasets indicated reduced klotho mRNA levels in human colorectal cancer, along with negative regulation of klotho expression by hypermethylation of the promoter and 1st exon, and hypomethylation of an area within the gene. Overexpression or treatment with klotho or KL1 inhibited proliferation of colorectal cancer cells in vitro. The in vivo activity of klotho and KL1 was examined using two models recapitulating development of tumors in the normal colonic environment of immune-competent mice. Treatment with klotho inhibited formation of colon polyps induced by the carcinogen azoxymethane, and KL1 treatment slowed growth of orthotopically-implanted colorectal tumors. Gene expression array revealed that klotho and KL1 expression enhanced the unfolded protein response (UPR) and this was further established by increased levels of spliced XBP1, GRP78 and phosphorylated-eIF2α. Furthermore, attenuation of the UPR partially abrogated klotho tumor suppressor activity. In conclusion, this study indicates klotho as a tumor suppressor in colorectal cancer and identifies, for the first time, the UPR as a pathway mediating klotho activities in cancer. These data suggest that administration of exogenous klotho or KL1 may serve as a novel strategy for prevention and treatment of colorectal cancer.
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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.