<i>Solobacterium moorei</i> promotes tumor progression via the Integrin α2/β1-PI3K-AKT-mTOR-C-myc signaling pathway in colorectal cancer

More and more evidences show that the imbalance of intestinal flora homeostasis can contribute to the progression of colorectal cancer (CRC). <i>Solobacterium moorei (S. moorei)</i>, an anaerobic Gram-positive bacillus, was found to be enriched in fecal samples from CRC patients. However, the signaling regulatory mechanism of <i>S. moorei</i> promoting CRC progression remain unknown. Three CRC mouse models (<i>Apc^Min/+</i> mice, AOM/DSS-treated mice and subcutaneous colorectal xenograft mice) and two cell lines (DLD-1 and HT-29) were used to investigate the biological functions and molecular mechanisms of <i>S. moorei</i> on tumor progression of CRC <i>in vivo</i> and <i>in vitro</i>. <i>S. moorei</i> abundance increased in fecal samples and tumor tissues, and was significantly positively correlated with tumor staging of CRC. <i>S. moorei</i> promoted tumor progression in various CRC mouse models and it selectively adhered to cancer cells in comparison to colonic mucosal epithelial cells, enhancing CRC cell proliferation and inhibiting cell apoptosis. Mechanistically, <i>S. moorei</i> cellwall protein Cna B-type domain-containing protein binds to integrin α2/β1 on CRC cells, leading to the activation of PI3K-AKT-mTOR-C-myc pathway via phospho-FAK, thereby promoted tumor cell growth and progression. Blockade of integrin α2/β1 abolished <i>S. moorei</i>-mediated oncogenic response <i>in vitro</i> and <i>in vivo</i>. In summary, this study demonstrated that <i>S. moorei</i> promoted tumor progression via the integrin α2/β1-PI3K-AKT-mTOR-C-myc signaling pathway, which is a novel specific pathogen-mediated mechanism that might be a new potential target for CRC prevention, diagnosis, and treatment.