Helicobacter Pylori Targets the EPHA2 Receptor Tyrosine Kinase in Gastric Cells Modulating Key Cellular Functions

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Leite, M (Author) Other; Marques, MS (Author) Other; Melo, J (Author) Other; Pinto, MT (Author) Other; Cavadas, B (Author) Other; Aroso, M (Author) Other; Gomez Lazaro, M (Author) Other; Seruca, R (Author) Other; Figueiredo C (Author) FMUP

Journal

Title: Cells

Vol. 26

Final page: 513

ISSN: 2073-4409

Publisher: MDPI

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 17 Citations

Other information

Authenticus ID: P-00R-Z1C

DOI: 10.3390/cells9020513

Abstract (EN): Helicobacter pylori, a stomach-colonizing Gram-negative bacterium, is the main etiological factor of various gastroduodenal diseases, including gastric adenocarcinoma. By establishing a life-long infection of the gastric mucosa, H. pylori continuously activates host-signaling pathways, in particular those associated with receptor tyrosine kinases. Using two different gastric epithelial cell lines, we show that H. pylori targets the receptor tyrosine kinase EPHA2. For long periods of time post-infection, H. pylori induces EPHA2 protein downregulation without affecting its mRNA levels, an effect preceded by receptor activation via phosphorylation. EPHA2 receptor downregulation occurs via the lysosomal degradation pathway and is independent of the H.pylori virulence factors CagA, VacA, and T4SS. Using small interfering RNA, we show that EPHA2 knockdown affects cell-cell and cell-matrix adhesion, invasion, and angiogenesis, which are critical cellular processes in early gastric lesions and carcinogenesis mediated by the bacteria. This work contributes to the unraveling of the underlying mechanisms of H. pylori-host interactions and associated diseases. Additionally, it raises awareness for potential interference between H. pylori infection and the efficacy of gastric cancer therapies targeting receptors tyrosine kinases, given that infection affects the steady-state levels and dynamics of some receptor tyrosine kinases (RTKs) and their signaling pathways.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 22