ArticleOncogene2020
Klotho rewires cellular metabolism of breast cancer cells through alteration of calcium shuttling and mitochondrial activity.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Calcium dysregulation in breast cancer progression: mechanisms of calcicoptosis and therapeutic implications.Cancer gene therapy · 2026Review
- α-Klotho as a central integrative signalling hub in cognitive function and neuroprotection in neurodegenerative diseases.Metabolic brain disease · 2026Review
- Breast Cancer Progression by the FGF/FGFR Axis: A Metabolic Perspective.Journal of mammary gland biology and neoplasia · 2025Review
- Construction of a prognostic model for lung adenocarcinoma based on necroptosis genes and its exploration of the potential for tumor immunotherapy.Translational cancer research · 2025Article
- Klotho protein: a multifaceted regulator in aging and cancer dynamics.Molecular biology reports · 2025Review
- Article
- Growth and development of the mammary gland in mice-control of the insulin-like growth factor system by hormones and metalloproteases, and putative interference with micro RNAs.Animal frontiers : the review magazine of animal agriculture · 2023Article
- The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.Life (Basel, Switzerland) · 2023Review
- Article
- Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Association of serum Klotho levels with cancer and cancer mortality: Evidence from National Health and Nutrition Examination Survey.Cancer medicine · 2023Article
- Article
- Review
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer's Disease: A Review.Biomedicines · 2022Review
- Alginate Oligosaccharide Ameliorates D-Galactose-Induced Kidney Aging in Mice through Activation of the Nrf2 Signaling Pathway.BioMed research international · 2021Article
- 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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klotho is a transmembrane protein, which can be shed and act as a circulating hormone and is involved in regulating cellular calcium levels and inhibition of the PI3K/AKT pathway. As a longevity hormone, it protects normal cells from oxidative stress, and as a tumor suppressor it inhibits growth of cancer cells. Mechanisms governing these differential activities have not been addressed. Altered cellular metabolism is a hallmark of cancer and dysregulation of mitochondrial activity is a hallmark of aging. We hypothesized that klotho exerts its differential effects through regulation of these two hallmarks. Treatment with klotho inhibited glycolysis, reduced mitochondrial activity and membrane potential only in cancer cells. Accordingly, global metabolic screen revealed that klotho altered pivotal metabolic pathways, amongst them glycolysis and tricarboxylic acid cycle in breast cancer cells. Alteration of metabolic activity and increased AMP/ATP ratio lead to LKB1-dependent AMPK activation. Indeed, klotho induced AMPK phosphorylation; furthermore, inhibition of LKB1 partially abolished klotho's tumor suppressor activity. By diminishing deltapsi (Δψ) klotho also inhibited mitochondria Ca
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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 Socratic graph.