Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma
Abstract The epithelial‐to‐mesenchymal transition (EMT) plays a central role in the development of cancer metastasis and resistance to chemotherapy. However, its pharmacological treatment remains challenging. Here, we used an EMT‐focused integrative functional genomic approach and identified an inve...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-12-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202317836 |
| _version_ | 1797279720137555968 |
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| author | Vignesh Ramesh Paradesi Naidu Gollavilli Luisa Pinna Mohammad Aarif Siddiqui Adriana Martinez Turtos Francesca Napoli Yasmin Antonelli Aldo Leal‐Egaña Jesper Foged Havelund Simon Toftholm Jakobsen Elisa Le Boiteux Marco Volante Nils Joakim Færgeman Ole N Jensen Rasmus Siersbæk Kumar Somyajit Paolo Ceppi |
| author_facet | Vignesh Ramesh Paradesi Naidu Gollavilli Luisa Pinna Mohammad Aarif Siddiqui Adriana Martinez Turtos Francesca Napoli Yasmin Antonelli Aldo Leal‐Egaña Jesper Foged Havelund Simon Toftholm Jakobsen Elisa Le Boiteux Marco Volante Nils Joakim Færgeman Ole N Jensen Rasmus Siersbæk Kumar Somyajit Paolo Ceppi |
| author_sort | Vignesh Ramesh |
| collection | DOAJ |
| description | Abstract The epithelial‐to‐mesenchymal transition (EMT) plays a central role in the development of cancer metastasis and resistance to chemotherapy. However, its pharmacological treatment remains challenging. Here, we used an EMT‐focused integrative functional genomic approach and identified an inverse association between short‐chain fatty acids (propionate and butanoate) and EMT in non‐small cell lung cancer (NSCLC) patients. Remarkably, treatment with propionate in vitro reinforced the epithelial transcriptional program promoting cell‐to‐cell contact and cell adhesion, while reducing the aggressive and chemo‐resistant EMT phenotype in lung cancer cell lines. Propionate treatment also decreased the metastatic potential and limited lymph node spread in both nude mice and a genetic NSCLC mouse model. Further analysis revealed that chromatin remodeling through H3K27 acetylation (mediated by p300) is the mechanism underlying the shift toward an epithelial state upon propionate treatment. The results suggest that propionate administration has therapeutic potential in reducing NSCLC aggressiveness and warrants further clinical testing. |
| first_indexed | 2024-03-07T16:31:07Z |
| format | Article |
| id | doaj.art-f6a02b7c4b9e494a97d706c0ba7228b7 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:31:07Z |
| publishDate | 2023-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-f6a02b7c4b9e494a97d706c0ba7228b72024-03-03T11:22:13ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-12-011512n/an/a10.15252/emmm.202317836Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinomaVignesh Ramesh0Paradesi Naidu Gollavilli1Luisa Pinna2Mohammad Aarif Siddiqui3Adriana Martinez Turtos4Francesca Napoli5Yasmin Antonelli6Aldo Leal‐Egaña7Jesper Foged Havelund8Simon Toftholm Jakobsen9Elisa Le Boiteux10Marco Volante11Nils Joakim Færgeman12Ole N Jensen13Rasmus Siersbæk14Kumar Somyajit15Paolo Ceppi16Department of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Oncology at San Luigi Hospital University of Turin Turin ItalyInstitute for Molecular Systems Engineering and Advanced Materials Heidelberg University Heidelberg GermanyInstitute for Molecular Systems Engineering and Advanced Materials Heidelberg University Heidelberg GermanyDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Oncology at San Luigi Hospital University of Turin Turin ItalyDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkDepartment of Biochemistry and Molecular Biology University of Southern Denmark Odense DenmarkAbstract The epithelial‐to‐mesenchymal transition (EMT) plays a central role in the development of cancer metastasis and resistance to chemotherapy. However, its pharmacological treatment remains challenging. Here, we used an EMT‐focused integrative functional genomic approach and identified an inverse association between short‐chain fatty acids (propionate and butanoate) and EMT in non‐small cell lung cancer (NSCLC) patients. Remarkably, treatment with propionate in vitro reinforced the epithelial transcriptional program promoting cell‐to‐cell contact and cell adhesion, while reducing the aggressive and chemo‐resistant EMT phenotype in lung cancer cell lines. Propionate treatment also decreased the metastatic potential and limited lymph node spread in both nude mice and a genetic NSCLC mouse model. Further analysis revealed that chromatin remodeling through H3K27 acetylation (mediated by p300) is the mechanism underlying the shift toward an epithelial state upon propionate treatment. The results suggest that propionate administration has therapeutic potential in reducing NSCLC aggressiveness and warrants further clinical testing.https://doi.org/10.15252/emmm.202317836epithelial–mesenchymal transitionH3K27 acetylationmetastasismetabolic inhibitorpropionate |
| spellingShingle | Vignesh Ramesh Paradesi Naidu Gollavilli Luisa Pinna Mohammad Aarif Siddiqui Adriana Martinez Turtos Francesca Napoli Yasmin Antonelli Aldo Leal‐Egaña Jesper Foged Havelund Simon Toftholm Jakobsen Elisa Le Boiteux Marco Volante Nils Joakim Færgeman Ole N Jensen Rasmus Siersbæk Kumar Somyajit Paolo Ceppi Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma EMBO Molecular Medicine epithelial–mesenchymal transition H3K27 acetylation metastasis metabolic inhibitor propionate |
| title | Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma |
| title_full | Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma |
| title_fullStr | Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma |
| title_full_unstemmed | Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma |
| title_short | Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma |
| title_sort | propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma |
| topic | epithelial–mesenchymal transition H3K27 acetylation metastasis metabolic inhibitor propionate |
| url | https://doi.org/10.15252/emmm.202317836 |
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