Propionate Reinforces Epithelial Identity and Reduces Aggressiveness of Lung Carcinoma

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2023 Sep 28

PMID 37766669

Authors

Vignesh Ramesh

Paradesi Naidu Gollavilli

Luisa Pinna

Mohammad Aarif Siddiqui

Adriana Martinez Turtos

Francesca Napoli

Yasmin Antonelli

Aldo Leal-Egana

Jesper Foged Havelund

Simon Toftholm Jakobsen

Elisa Le Boiteux

Marco Volante

Nils Joakim Faergeman

Ole N Jensen

Rasmus Siersbaek

Kumar Somyajit

Paolo Ceppi

Affiliations

Soon will be listed here.

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.

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Propionate reinforces epithelial identity and reduces aggressiveness of lung carcinoma.

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