| Title: |
Nrf2 Downregulation Contributes to Epithelial-to-Mesenchymal Transition in Helicobacter pylori-Infected Cells |
| Authors: |
Bacon, Sarah; Seeneevassen, Lornella; Fratacci, Alison; Rose, Faustine; Tiffon, Camille; Sifre, Elodie; Haykal, Maria M.; Moubarak, Maya M.; Ducournau, Astrid; Bruhl, Lucie; Claverol, Stephane; Tokarski, Caroline; Gouloumi, Alina-Roxani; Pateras, Ioannis S.; Daubon, Thomas; Lehours, Philippe; Varon, Christine; Martin, Oceane C. B. |
| Contributors: |
BoRdeaux Institute of onCology (Inserm U1312 - BRIC); Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM); Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO (U981)); Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Université de Bordeaux (UB); Chimie et Biologie des Membranes et des Nanoobjets (CBMN); Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); National and Kapodistrian University of Athens (NKUA); Institut de biochimie et génétique cellulaires (IBGC); Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 2072-6694. |
| Publisher Information: |
CCSD; MDPI |
| Publication Year: |
2022 |
| Subject Terms: |
Gastric cancer; Helicobacter pylori; Nrf2; Redox homeostasis; Epithelial-to-mesenchymal transition; [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases |
| Description: |
International audience ; Background: Gastric cancer, the fifth most common cancer worldwide, is mainly linked to Helicobacter pylori infection. H. pylori induces chronic inflammation of the gastric mucosa associated with high oxidative stress. Our study aimed at assessing the implication of Nrf2, a major regulator of cellular redox homeostasis, in H. pylori-induced gastric carcinogenesis.Methods: Using three different gastric epithelial cell lines, a non-cancerous (HFE-145) and two different subtypes of gastric cancer (AGS and MKN74), we analyzed the modulation of Nrf2 expression over time. After invalidation of Nrf2 by CRISPR-cas9, we assessed its role in H. pylori-induced epithelial-to-mesenchymal transition (EMT). Finally, we evaluated the expression of Nrf2 and ZEB1, a central EMT transcription factor, in human gastric tissues.Results: We first demonstrated that the Nrf2 signaling pathway is differentially regulated depending on the infection stage. Rapidly and transiently activated, Nrf2 was downregulated 24 h post-infection in a VacA-dependent manner. We then demonstrated that Nrf2 invalidation leads to increased EMT, which is even exacerbated after H. pylori infection. Finally, Nrf2 expression tended to decrease in human patients’ gastric mucosa infected with H. pylori.Conclusions: Our work supports the hypothesis that Nrf2 downregulation upon H. pylori infection participates in EMT, one of the most important events in gastric carcinogenesis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.3390/cancers14174316 |
| Availability: |
https://hal.science/hal-04082414; https://hal.science/hal-04082414v1/document; https://hal.science/hal-04082414v1/file/CBMN_Cancers_2022_Bacon.pdf; https://doi.org/10.3390/cancers14174316 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.EC0BCD56 |
| Database: |
BASE |