Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma

Wei Cheng Lin, Huei-Fang Tsai, Sung Hsin Kuo, Ming Shiang Wu, Chung Wu Lin, Ping I. Hsu, Ann Lii Cheng, Ping Ning Hsu

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Abstract

Infection by cagA-positive Helicobacter pylori (H. pylori) is strongly associated with gastric carcinomas and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. H. pylori translocates the bacterial protein CagA into gastric epithelial cells, and the translocated CagA deregulates intracellular signaling pathways and thereby initiates pathogenesis. This in turn raised the possibility that H. pylori is associated with the development of MALT lymphomas during persistent infection by direct interaction with B lymphocytes. In this work, we showed that CagA can be directly translocated into human B lymphoid cells by H. pylori, and the translocated CagA undergoes tyrosine phosphorylation and binds to intracellular SH-2. Meanwhile, the translocated CagA induces activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in human B lymphoid cells, and upregulates the expressions of Bcl-2 and Bcl-XL, which prevents apoptosis. These results provide the first direct evidence for the role of CagA as a bacterium-derived oncoprotein that acts in human B cells, and further implies that CagA is directly delivered into B cells by H. pylori and is associated with the development of MALT lymphomas.

Original languageEnglish
Pages (from-to)5740-5748
Number of pages9
JournalCancer Research
Volume70
Issue number14
DOIs
Publication statusPublished - Jul 15 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Lin, W. C., Tsai, H-F., Kuo, S. H., Wu, M. S., Lin, C. W., Hsu, P. I., Cheng, A. L., & Hsu, P. N. (2010). Translocation of Helicobacter pylori CagA into human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma. Cancer Research, 70(14), 5740-5748. https://doi.org/10.1158/0008-5472.CAN-09-4690