Enterococcus faecalis promotes a migratory and invasive phenotype in colon cancer cells

• Published in: Neoplasia (New York, N.Y.) Vol. 27; p. 100787
• Main Authors: Williamson, Ashley J., Jacobson, Rick, van Praagh, J.B., Gaines, Sara, Koo, Hyun Y., Lee, Brandon, Chan, Wen-Ching, Weichselbaum, Ralph, Alverdy, John C., Zaborina, Olga, Shogan, Benjamin D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2022; Neoplasia Press; Elsevier
• Subjects: Animals; Collagenases - metabolism; Colon cancer; Colonic Neoplasms - genetics; Enterococcus faecalis; Enterococcus faecalis - genetics; Enterococcus faecalis - metabolism; gelE; Humans; Mice; Original article; Phenotype; uPA; uPAR; Urokinase-Type Plasminogen Activator - metabolism; Enterococcus faecalis; uPAR; Colon cancer; gelE; uPA
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2022.100787

Much about the role of intestinal microbes at the site of colon cancer development and tumor progression following curative resection remains to be understood. We have recently shown that collagenolytic bacteria such as Enterococcus faecalis predominate within the colon postoperatively, particularly at the site of the colon reconnection (i.e. anastomosis) in the early period of post-surgical recovery. The presence of collagenolytic bacteria at this site correlates with the tumor progression in a mouse model of post-surgical tumor development. In the present study we hypothesized, that collagenolytic bacteria, such as E. faecalis, play an important yet to be discovered role in tumor formation and progression. Therefore the aims of this study were to assess the role of collagenolytic E. faecalis on the migration and invasion of a murine colon cancer cell line. Results demonstrated that both migration and invasion were induced by E. faecalis with collagenolytic activity being required for only invasion. Bidirectional signaling in the E. faecalis-cancer cell interaction was observed by the discovering that the expression of gelE in E. faecalis, the gene required for collagenase production, is expressed in response to exposure to CT26 cells. The mechanism by which migration enhancement via E. faecalis occurs appears to be dependent on its ability to activate pro-uPA, a key element of the urokinase-plasminogen system, a pathway that is well – known to be important in cancer cell invasion and migration. Finally, we demonstrated that collagenase producing microbes preferentially colonize human colon cancer specimens.