Buchumschlag

Functional antagonism between CagA and DLC1 in gastric cancer

Helicobacter (H.) pylori-induced gastritis is a risk factor for gastric cancer (GC). Deleted-in-liver-cancer-1 (DLC1/ARHGAP7) inhibits RHOA, a downstream mediator of virulence factor cytotoxin-A (CagA) signalling and driver of consensus-molecular-subtype-2 diffuse GC. DLC1 located to enterochromaffi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Hinsenkamp, Isabel (VerfasserIn) , Köhler, Jan Philipp (VerfasserIn) , Flächsenhaar, Christoph (VerfasserIn) , Hitkova, Ivana (VerfasserIn) , Meessen, Sabine Eberhart (VerfasserIn) , Gaiser, Timo (VerfasserIn) , Wieland, Thomas (VerfasserIn) , Weiß, Christel (VerfasserIn) , Röcken, Christoph (VerfasserIn) , Mowat, Michael (VerfasserIn) , Quante, Michael (VerfasserIn) , Taxauer, Karin (VerfasserIn) , Mejías-Luque, Raquel (VerfasserIn) , Gerhard, Markus (VerfasserIn) , Vogelmann, Roger (VerfasserIn) , Meindl-Beinker, Nadja M. (VerfasserIn) , Ebert, Matthias (VerfasserIn) , Burgermeister, Elke (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 13 August 2022
In: Cell death discovery
Year: 2022, Jahrgang: 8, Pages: 1-12
ISSN:2058-7716
DOI:10.1038/s41420-022-01134-x
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41420-022-01134-x
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41420-022-01134-x
Volltext
Verfasserangaben:Isabel Hinsenkamp, Jan P. Köhler, Christoph Flächsenhaar, Ivana Hitkova, Sabine Eberhart Meessen, Timo Gaiser, Thomas Wieland, Christel Weiss, Christoph Röcken, Michael Mowat, Michael Quante, Karin Taxauer, Raquel Mejias-Luque, Markus Gerhard, Roger Vogelmann, Nadja Meindl-Beinker, Matthias Ebert and Elke Burgermeister
Beschreibung
Zusammenfassung:Helicobacter (H.) pylori-induced gastritis is a risk factor for gastric cancer (GC). Deleted-in-liver-cancer-1 (DLC1/ARHGAP7) inhibits RHOA, a downstream mediator of virulence factor cytotoxin-A (CagA) signalling and driver of consensus-molecular-subtype-2 diffuse GC. DLC1 located to enterochromaffin-like and MIST1+ stem/chief cells in the stomach. DLC1+ cells were reduced in H. pylori gastritis and GC, and in mice infected with H. pylori. DLC1 positivity inversely correlated with tumour progression in patients. GC cells retained an N-terminal truncation variant DLC1v4 in contrast to full-length DLC1v1 in non-neoplastic tissues. H. pylori and CagA downregulated DLC1v1/4 promoter activities. DLC1v1/4 inhibited cell migration and counteracted CagA-driven stress phenotypes enforcing focal adhesion. CagA and DLC1 interacted via their N- and C-terminal domains, proposing that DLC1 protects against H. pylori by neutralising CagA. H. pylori-induced DLC1 loss is an early molecular event, which makes it a potential marker or target for subtype-aware cancer prevention or therapy.
Beschreibung:Gesehen am 23.10.2023
Beschreibung:Online Resource
ISSN:2058-7716
DOI:10.1038/s41420-022-01134-x

Ähnliche Einträge