ArticleCell death & disease2022
Metformin suppresses the growth of colorectal cancer by targeting INHBA to inhibit TGF-β/PI3K/AKT signaling transduction.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 82 citations in OpenAlex.
- Transforming growth factor beta-related proteins promote axonal regeneration of injured dorsal root ganglion neurons.Neural regeneration research · 2026Article
- DPP-4 Inhibitors in Female Cancers: Opportunities for Drug Repurposing.Current issues in molecular biology · 2026Review
- Unbiased profiling of translational landscape reveals TNFR2 as a translation-dependent vulnerability in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Metformin in gastrointestinal cancers and inflammatory bowel disease: Unraveling its mechanisms and therapeutic applications.iScience · 2026Review
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- Pharmacological mechanisms and clinical impacts of antidiabetic drugs on colorectal cancer risk: a systematic review.Frontiers in pharmacology · 2026Review
- INHBA Promotes the Progression of Gastric Cancer by Activating MAPK Signaling Pathway via Targeting ITGA6.Oncology research · 2026Article
- Inhibin beta A drives colorectal cancer progression through macrophage M2 polarization and mitochondria-dependent ferroptosis suppression.Signal transduction and targeted therapy · 2025Article
- Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.Molecular biomedicine · 2025Article
- Fundamental role of brain-organ interaction in behavior-driven holistic homeostasis.Fundamental research · 2025Review
- Genetic variants linked to type 2 diabetes in CDKN1B and TCF7L2 influence survival outcomes in metastatic colorectal cancer.International journal of cancer · 2025Article
- Article
- Metformin facilitates osteogenic differentiation of bone marrow stromal cells through AMPK-dependent autophagy: an investigation into the healing of osteoporotic fractures in murine models.Journal of orthopaedic surgery and research · 2025Article
- Metformin in Colorectal Cancer: Epidemiological Evidence, Predictive Biomarkers, and Implications for Prevention and Treatment.International journal of molecular sciences · 2025Review
- Phospholipase D6 activates Wnt/β-catenin signaling through mitochondrial metabolic reprogramming to promote tumorigenesis in colorectal cancer.Experimental & molecular medicine · 2025Article
- Metformin inhibits the growth of SCLC cells by inducing autophagy and apoptosis via the suppression of EGFR and AKT signalling.Scientific reports · 2025Article
- Review
- Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability.Cell & bioscience · 2025Article
- Metformin exerted tumoricidal effects on colon cancer tumoroids via the regulation of autophagy pathway.Stem cell research & therapy · 2025Article
- Fasting in combination with the cocktail Sorafenib:Metformin blunts cellular plasticity and promotes liver cancer cell death via poly-metabolic exhaustion.Cellular oncology (Dordrecht, Netherlands) · 2025Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple evidence shows that metformin serves as a potential agent for Colorectal Cancer (CRC) treatment, while its molecular mechanisms still require detailed investigation. Here, we revealed that metformin specifically suppressed the proliferation of CRC cells by causing G1/S arrest, and INHBA is a potential target for metformin to play an anti-proliferation effect in CRC. We verified the oncogene role of INHBA by knocking down and overexpressing INHBA in CRC cells. Silencing INHBA abrogated the cell growth, while overexpression INHBA promotes the proliferation of CRC cells. As an oncogene, INHBA was aberrant overexpression in CRC tissues and closely related to the poor prognosis of CRC patients. In mechanism, INHBA is an important ligand of TGF-β signaling and metformin blocked the activation of TGF-β signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest. Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-β/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC. Our study elucidated a novel molecular mechanism for the anti-proliferation effect of metformin, providing a theoretical basis for the application of metformin in CRC therapy.
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