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Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

Oncogene volume 27, pages 7047–7054 (2008)Cite this article

Abstract

Loss of cell polarity and tissue architecture is a hallmark of carcinomas that arise from epithelial cells. Recent studies on Drosophila tumor suppressors have provided evidence that epithelial polarity and cell proliferation are functionally coupled, suggesting a function for polarity defects in the development of carcinomas. This notion is supported by the findings that mammalian orthologs of these Drosophila tumor suppressors are targeted by a number of viral oncoproteins. Chronic infection with Helicobacter pylori is causally associated with gastric carcinoma. H. pylori virulence factor CagA (cytotoxin-associated gene A), which is delivered into gastric epithelial cells through a bacterial type IV secretion system, has an important function in cell transformation through interacting with and deregulating SHP-2 phosphatase, a bona fide oncoprotein that is associated with human malignancies. Recent studies have further revealed that CagA specifically binds and inhibits PAR1/MARK polarity-regulating kinase, thereby causing junctional and polarity defects in epithelial cells. Thus, the bacterial oncoprotein simultaneously targets the polarity-regulating system and growth-regulatory system. These findings indicate that loss of cell polarity underlies the abnormal proliferation of epithelial cells that directs carcinogenesis.

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Hatakeyama, M. Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA. Oncogene 27, 7047–7054 (2008). https://doi.org/10.1038/onc.2008.353

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