Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells
Fazio C, Piazzi G, Vitaglione P, Fogliano V, Munarini A, Prossomariti A, Milazzo M, D'Angelo L, Napolitano M, Chieco P, Belluzzi A, Bazzoli F, Ricciardiello L
Scientific reports · 42 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Funding not disclosed
Publication
- Published
- 2016-02-11 · Sci Rep · vol. 6 · issue 1 · p. 20670
- Publisher
- Nature Portfolio
- Cited
- 52 citations · more than 89% of similar papers · 2.7× the field average
- References
- 53 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Cancer, Hypoxia, and Metabolism · Cancer, Lipids, and Metabolism · Cancer-related molecular mechanisms research
- Keywords
- Eicosapentaenoic acid, Inflammation, MMP9, Cancer research, Colorectal cancer, Chemistry, Polyunsaturated fatty acid, Downregulation and upregulation, Cancer, Fatty acid, Biology, Medicine, Immunology, Biochemistry, Internal medicine
- MeSH
- monocytes, cell line, hct116 cells, ht29 cells, humans, inflammation, tetradecanoylphorbol acetate, lipopolysaccharides, eicosapentaenoic acid, cytokines, culture media, conditioned, signal transduction, cell differentiation, cell movement, gene expression regulation, receptor, notch1, matrix metalloproteinase 9, epithelial-mesenchymal transition
13 authors
From IT, NL
- Chiara Di FazioIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Giulia PiazziIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Paola VitaglioneUniversity of Naples Federico II
- Vincenzo FoglianoWageningen University & Research
- Alessandra MunariniIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
- Anna ProssomaritiIRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola; University of Bologna
Abstract
Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.