ArticleBritish journal of cancer2021
Kinome-wide analysis of the effect of statins in colorectal cancer.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Atorvastatin promotes lipid catabolism in colorectal cancer via FDFT1‒mediated inhibition of the PI3K/AKT pathway.Cell communication and signaling : CCS · 2026Article
- A Clinical Analysis of the Association Between Nifedipine and Insulin Usage and the Increased Incidence of Colonic Polyps.JGH open : an open access journal of gastroenterology and hepatology · 2025Article
- A Biochemical View on Intermittent Fasting's Effects on Human Physiology-Not Always a Beneficial Strategy.Biology · 2025Review
- Targeting PAR-2-driven inflammatory pathways in colorectal cancer: mechanistic insights from atorvastatin and rosuvastatin treatment in cell line models.Translational cancer research · 2025Article
- Statins regulate kinase signaling by causing changes in phosphorylation, rather than through changes in gene expression or direct inhibition: evidence in colorectal cancer.Frontiers in pharmacology · 2025Article
- Stromal BMP signaling regulates mucin production in the large intestine via interleukin-1/17.Science advances · 2023Article
- The Sterol Transporter Npc2c Controls Intestinal Stem Cell Mitosis and Host-Microbiome Interactions inMetabolites · 2023Article
- Statins block mammalian target of rapamycin pathway: a possible novel therapeutic strategy for inflammatory, malignant and neurodegenerative diseases.Inflammopharmacology · 2023Review
- Chronic Obstructive Pulmonary Disease Increases the Risk of Mortality among Patients with Colorectal Cancer: A Nationwide Population-Based Retrospective Cohort Study.International journal of environmental research and public health · 2021Article
- Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage.Frontiers in immunology · 2021Article
- Targeting the Tumor Microenvironment: A Literature Review of the Novel Anti-Tumor Mechanism of Statins.Frontiers in oncology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpidemiological studies and meta-analyses show an association between statin use and a reduced incidence of colorectal cancer (CRC). We have shown that statins act on CRC through bone morphogenetic protein (BMP) signalling, but the exact cellular targets and underlying mechanism of statin action remain elusive. In this study, we set out to assess the influence of statins on global cancer cell signalling by performing an array-based kinase assay using immobilised kinase substrates spanning the entire human kinome.
methodsCRC cells with or without Lovastatin treatment were used for kinome analysis. Findings on kinome arrays were further confirmed by immunoblotting with activity-specific antibodies. Experiments in different CRC cell lines using immunoblotting, siRNA-mediated knockdown and treatment with specific BMP inhibitor Noggin were performed. The relevance of in vitro findings was confirmed in xenografts and in CRC patients treated with Simvastatin.
resultsKinome analysis can distinguish between non-specific, toxic effects caused by 10 µM of Lovastatin and specific effects on cell signalling caused by 2 µM Lovastatin. Statins induce upregulation of PTEN activity leading to downregulation of the PI3K/Akt/mTOR signalling. Treatment of cells with the specific BMP inhibitor Noggin as well as PTEN knockdown and transfection of cells with a constitutively active form of AKT abolishes the effect of Lovastatin on mTOR phosphorylation. Experiments in xenografts and in patients treated with Simvastatin confirm statin-mediated BMP pathway activation, activation of PTEN and downregulation of mTOR signalling.
conclusionsStatins induce BMP-specific activation of PTEN and inhibition of PI3K/Akt/mTOR signalling in CRC.
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