ArticleJournal of cellular and molecular medicine2021
AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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
16 citing papers in PubMed, 22 citations in OpenAlex.
- TGF-beta inhibitors in cancer therapy: a review of the TGF-beta signal transduction pathway and current developments.EXCLI journal · 2026Review
- Clinical significance of the S204 phosphorylation of the Smad3 protein in combination with Ki67 for the metastasis and prognosis of gastric cancer.BMC gastroenterology · 2025Observational
- Mendelian randomization and mediation analysis reveal the role of immune cells in the pathways between inflammatory factors and glioblastoma.The Journal of international medical research · 2025Article
- SMAD3 orchestrates RNF167 and STAMBPL1-mediated Sestrin2 ubiquitination to drive gastric cancer progression.Cell division · 2025Article
- Article
- Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.World journal of gastrointestinal oncology · 2024Article
- [High expression of RAB7A is associated with poor prognosis of gastric cancer by promoting tumor invasion].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Article
- A model for the dissemination of circulating tumour cell clusters involving platelet recruitment and a plastic switch between cooperative and individual behaviours.BMC ecology and evolution · 2023Article
- Mechanism Underlying Metformin Action and Its Potential to Reduce Gastric Cancer Risk.International journal of molecular sciences · 2022Review
- Cancer Stem Cells in Tumor Microenvironment of Adenocarcinoma of the Stomach, Colon, and Rectum.Cancers · 2022Review
- Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management.Journal of hematology & oncology · 2022Review
- Chronic Intermittent Hypoxia Exposure Alternative to Exercise Alleviates High-Fat-Diet-Induced Obesity and Fatty Liver.International journal of molecular sciences · 2022Article
- MicroRNA MiR-130a-3p promotes gastric cancer by targeting Glucosaminyl N-acetyl transferase 4 (GCNT4) to regulate the TGF-β1/SMAD3 pathway.Bioengineered · 2021Article
- AMPK inhibits Smad3-mediated autoinduction of TGF-β1 in gastric cancer cells.Journal of cellular and molecular medicine · 2021Article
- Regulation and Signaling of TGF-β Autoinduction.International journal of molecular and cellular medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that adenine monophosphate-activated protein kinase (AMPK) regulates transforming growth factor β (TGF-β)-triggered Smad3 phosphorylation. Here we report that AMPK inhibits TGF-β1 production. First, metformin reduced mRNA levels of TGF-β1 in gastric cancer cells, in parallel to the decrease of its protein abundance. The effects were more prominent in the cells containing LKB1, an upstream kinase of AMPK. Second, knockdown of Smad3 by siRNA abrogated the expression of TGF-β1. Third, metformin suppressed firefly luciferase activity whose transcription was driven by TGF-β1 promoter. In accordance, deletion of the putative binding site of Smad3 in the TGF-β1 promoter region severely impaired the promoter activity and response to metformin. Fourth, in support of our in vitro study, clinical treatment of type 2 diabetes with metformin significantly reduced the plasma level of TGF-β1. Finally, immunohistochemical studies revealed that TGF-β1 was highly expressed in human gastric cancer tissues as compared with adjacent normal tissues. In contrast, p-AMPK exhibited opposite changes. Furthermore, the survival rate of gastric cancer patients was positively correlated with p-AMPK and negative with TGF-β1. Therefore, our present studies depict a mechanism underlying AMPK suppression of TGF-β1 autoinduction, which is mediated through inhibition of Smad3 phosphorylation and activation. Collectively, our study sheds a light on the potential usage of AMPK activators in the treatment of TGF-β1-mediated gastric cancer progression.
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.