<i>Solobacterium moorei</i> promotes tumor progression via the Integrin α2/β1-PI3K-AKT-mTOR-C-myc signaling pathway in colorectal cancer
Yan Chen, Ying� Qin, Tingting Fan, Cheng Qiu, Yijie Zhang, Mengmeng Dai, Yaoyao Zhou, Qinsheng Sun, Yuan Guo, Hao Yue, Yu‐Yang Jiang
Abstract
More and more evidences show that the imbalance of intestinal flora homeostasis can contribute to the progression of colorectal cancer (CRC).Solobacterium moorei (S. moorei), an anaerobic Gram-positive bacillus, was found to be enriched in fecal samples from CRC patients.However, the signaling regulatory mechanism of S. moorei promoting CRC progression remain unknown.Three CRC mouse models (Apc Min/+ 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 S. moorei on tumor progression of CRC in vivo and in vitro.S. moorei abundance increased in fecal samples and tumor tissues, and was significantly positively correlated with tumor staging of CRC. S. moorei 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, S. moorei cellwall protein Cna B-type domain-containing protein binds to integrin 2/1 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 2/1 abolished S. moorei-mediated oncogenic response in vitro and in vivo.In summary, this study demonstrated that S. moorei promoted tumor progression via the integrin 2/1-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.