ArticleCancer research2014
AMPK reverses the mesenchymal phenotype of cancer cells by targeting the Akt-MDM2-Foxo3a signaling axis.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 107 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- Dietary walnut altered gene expressions related to tumor growth, survival, and metastasis in breast cancer patients: a pilot clinical trial.Nutrition research (New York, N.Y.) · 2019Trial
- Ceritinib induces ferroptosis via TRIM21-mediated GLUT1 ubiquitination and AMPK-driven metabolic reprogramming in breast cancer.iScience · 2026Article
- Decreased AMP-kinase function in pulmonary artery smooth muscle cells contributes to pulmonary artery remodeling in persistent pulmonary hypertension of the newborn.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing.Discover oncology · 2025Article
- Rethinking AMPK: A Reversible Switch Fortifying Cancer Cell Stress-Resilience.The Yale journal of biology and medicine · 2025Review
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- METTL3-mediated mHeliyon · 2024Article
- AMPKα2 promotes tumor immune escape by inducing CD8+ T-cell exhaustion and CD4+ Treg cell formation in liver hepatocellular carcinoma.BMC cancer · 2024Article
- Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6.Journal of cancer research and clinical oncology · 2024Article
- Role and regulation of FOXO3a: new insights into breast cancer therapy.Frontiers in pharmacology · 2024Review
- Novel Adiponectin Receptor Agonist Inhibits Cholangiocarcinoma via Adenosine Monophosphate-activated Protein Kinase.Current medicinal chemistry · 2024Article
- Metformin as a PotentialInternational journal of breast cancer · 2024Review
- Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a.International journal of molecular sciences · 2023Article
- Obesity and prostate cancer - microenvironmental roles of adipose tissue.Nature reviews. Urology · 2023Review
- Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy.Cellular & molecular immunology · 2023Review
- Decoding the coupled decision-making of the epithelial-mesenchymal transition and metabolic reprogramming in cancer.iScience · 2023Article
- Impact of AMPK on cervical carcinoma progression and metastasis.Cell death & disease · 2023Article
- A combination of metformin and epigallocatechin gallate potentiates glioma chemotherapyFrontiers in pharmacology · 2023Article
- Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models.BJUI compass · 2023Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
- Correction · 2018-06-14Concerns/Issues about Image · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · · Ching Shih Chen has institutional finding of misconduct;
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
In cancer cells, the epithelial-mesenchymal transition (EMT) confers the ability to invade basement membranes and metastasize to distant sites, establishing it as an appealing target for therapeutic intervention. Here, we report a novel function of the master metabolic kinase AMPK in suppressing EMT by modulating the Akt-MDM2-Foxo3 signaling axis. This mechanistic link was supported by the effects of siRNA-mediated knockdown and pharmacologic activation of AMPK on epithelial and mesenchymal markers in established breast and prostate cancer cells. Exposure of cells to OSU-53, a novel allosteric AMPK activator, as well as metformin and AICAR, was sufficient to reverse their mesenchymal phenotype. These effects were abrogated by AMPK silencing. Phenotypic changes were mediated by Foxo3a activation, insofar as silencing or overexpressing Foxo3a mimicked the effects of AMPK silencing or OSU-53 treatment on EMT, respectively. Mechanistically, Foxo3a activation led to the transactivation of the E-cadherin gene and repression of genes encoding EMT-inducing transcription factors. OSU-53 activated Foxo3a through two Akt-dependent pathways, one at the level of nuclear localization by blocking Akt- and IKKβ-mediated phosphorylation, and a second at the level of protein stabilization via cytoplasmic sequestration of MDM2, an E3 ligase responsible for Foxo3a degradation. The suppressive effects of OSU-53 on EMT had therapeutic implications illustrated by its ability to block invasive phenotypes in vitro and metastatic properties in vivo. Overall, our work illuminates a mechanism of EMT regulation in cancer cells mediated by AMPK, along with preclinical evidence supporting a tractable therapeutic strategy to reverse mesenchymal phenotypes associated with invasion and metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.