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

Autores da FMUP
Participantes de fora da FMUP
- Leite, M
- Marques, MS
- Melo, J
- Pinto, MT
- Cavadas, B
- Aroso, M
- Gomez Lazaro, M
- Seruca, R
Unidades de investigação
Abstract
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.
Dados da publicação
- ISSN/ISSNe:
- 2073-4409, 2073-4409
- Tipo:
- Article
- Páginas:
- 513-
- DOI:
- 10.3390/cells9020513
- Link para outro recurso:
- www.scopus.com
Cells Multidisciplinary Digital Publishing Institute (MDPI)
Citações Recebidas na Web of Science: 18
Citações Recebidas na Scopus: 19
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- Não há documentos
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Keywords
- Helicobacter pylori; EPHA2; receptor tyrosine kinases (RTKs); angiogenesis; invasion; cell-cell adhesion; cell-matrix adhesion; RTK therapy; SRC inhibitors; gastric cancer
Campos de estudo
Proyectos asociados
Unravelling Helicobacter pylori strategies to disrupt cell-cell junctions
Investigador Principal: Maria do Céu Fontes Herdeiro Figueiredo
Estudo Clínico Académico (Helicobacter) . 2019
Citar a publicação
Leite M,Marques MS,Melo J,Pinto MT,Cavadas B,Aroso M,Gomez M,Seruca R,Figueiredo C. Helicobacter Pylori Targets the EPHA2 Receptor Tyrosine Kinase in Gastric Cells Modulating Key Cellular Functions. Cells. 2020. 26. (2):p. 513-513. IF:6,600. (2).