Porphyromonas gingivalis secreted factors drive EMT through gingipains and an H2S–mediated bacterial defense system
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Michal Kazelnik1, Michal Caspi1, Ilan Tsarfaty1, Elhanan Borenstein1,2, Konstantin Shatalin3, Evgeny Nudler3,4 and Rina Rosin-Arbesfeld1
1 Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. 2 Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel. 3 New York University Grossman School of Medicine, New York, NY 10016, USA. 4 Howard Hughes Medical Institute, New York, NY 10016, USA
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Dysbiosis of the gut microbiota is strongly associated with a large number of pathologies, including different cancer types. Porphyromonas gingivalis (P. gingivalis), an oral bacterium, has been shown to be closely related to the development of colorectal cancer (CRC). The exact mechanisms by which P. gingivalis contributes to CRC remain unclear, and emerging evidence suggests that various bacterial elements are involved in the bacterium's pathogenic effects. Here we show that P. gingivalis secreted factors promote CRC neoplasia progression by modulating both the Wnt/β-catenin and the Hippo-YAP signaling pathways. Specifically, our findings demonstrate that both gingipains, cysteine proteases implicated in the development of periodontitis, and hydrogen sulfide (Hâ‚‚S) strongly induce the expression of epithelial–mesenchymal transition (EMT) markers, leading to cell detachment and increased motility. These findings uncover a novel link between microbial virulence and defense mechanisms, such as Hâ‚‚S, and host cell transformation, highlighting a potential role for bacterial secreted factors in driving CRC neoplasia.