Streptococcus gallolyticus subsp. gallolyticus (Sg) has been reported to have a strong clinical correlation with colorectal cancer (CRC) for several decades. Our recent data indicates that Sg is able to actively promote the development of colon tumor and thus is also functionally important to CRC. Further investigations into the Sg-CRC connection revealed that there are variations among Sg strains with respect to their ability to stimulate target host cell proliferation and tumor growth. The ability of Sg to adhere to colon cancer cells and to colonize colonic epithelium in vivo appears to be important. The results suggest that direct interactions between specific Sg factors and colonic epithelial receptors/structures are required to trigger downstream signaling events leading to increased host cell proliferation. Furthermore, we observed that the effect of Sg is also dependent on the host genetic background, suggesting a dynamic and complex interactions between Sg and the host. In addition to the requirement for beta-catenin signaling as we previously reported, we observed that Sg activates yes-associated protein 1 (YAP1), a downstream effector in the Hippo signaling pathway. YAP1 activation is required for Sg to stimulate target host cell proliferation. YAP1 and the Hippo pathway are known to be involved in the development CRC. Bacterial activation of YAP1 has not been described before. Thus, our results suggest a novel mechanism by which bacteria contribute to the development of cancer. Studies are on-going to further investigate the molecular details of this mechanism.

Citation Format: Yi Xu, Ritesh Kumar, John Taylor, Juan Xu. Streptococcus gallolyticus in colorectal cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5141.