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Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma

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 assoc...

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Main Authors: Ramesh, Vignesh (Author) , Gollavilli, Paradesi Naidu (Author) , Pinna, Luisa (Author) , Siddiqui, Mohammad Aarif (Author) , Turtos, Adriana Martinez (Author) , Napoli, Francesca (Author) , Antonelli, Yasmin (Author) , Leal-Egaña, Aldo (Author) , Havelund, Jesper Foged (Author) , Jakobsen, Simon Toftholm (Author) , Boiteux, Elisa Le (Author) , Volante, Marco (Author) , Færgeman, Nils Joakim (Author) , Jensen, Ole N (Author) , Siersbæk, Rasmus (Author) , Somyajit, Kumar (Author) , Ceppi, Paolo (Author)
Format: Article (Journal)
Language:English
Published: 28 September 2023
In: EMBO molecular medicine
Year: 2023, Volume: 15, Issue: 12, Pages: 1-24
ISSN:1757-4684
DOI:10.15252/emmm.202317836
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.15252/emmm.202317836
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/emmm.202317836
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 25.01.2024
Physical Description:Online Resource
ISSN:1757-4684
DOI:10.15252/emmm.202317836

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