Non-canonical NF-ĸB signaling in H. pylori infection and gastric carcinogenesis

The activation of the non-canonical NF-κB pathway is linked to the development of different inflammation-driven tumors. We found that activation of non-canonical NF-κB signaling by H. pylori through lymphotoxin beta receptor (LTβR) is an essential mechanism driving chronic gastric inflammation (Mejías-Luque et al. Gut 2017), while LIGHT, another ligand activating non-canonical NF-κB is related to gastric pathology (Mejías-Luque et al. Sci Rep. 2019). Currently, we are further investigating this signaling pathway using different cellular and animal models. In particular, we are using gastric organoids to explore the effects of activating the pathway, and we generated a transgenic mouse model (LTαβTG), which specifically expresses LTα1β2 in the stomach under the control of the H+/K+ ATPase promoter. The analysis of cellular responses to the activation of non-canonical NF-κB will help us to elucidate the contribution of this important signaling cascade to gastric carcinogenesis.

Publications:

Mejías-Luque R, Lozano-Pope I, Wanisch A, Heikenwälder M, Gerhard M, Obonyo M. Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection. Sci Rep. 2019 May 7;9(1):7030. (Full Text; Abstract)

Mejías-Luque, R., J. Zoller, F. Anderl, E. Loew-Gil, M. Vieth, T. Adler, D.B. Engler, S. Urban, J.L. Browning, A. Muller, M. Gerhard, and M. Heikenwalder (2017). Lymphotoxin beta receptor signalling executes Helicobacter pylori-driven gastric inflammation in a T4SS-dependent manner. Gut. 66:1369-1381.(Full Text; Abstract)