Quorum-Sensing Regulator C8-HSL Promotes the Proliferation, Migration, and Invasion of Lung Cancer Cells by Activating the PI3K/AKT/ERK Pathway.

Lung microbiota has been proven to be closely related to lung cancer, but the precise mechanisms remain unclear. In this study, we found that the quorum-sensing regulator C8-HSL, secreted by Gram-negative bacteria, could promote the proliferation of H460 lung cancer cells in vitro and in vivo. C8-HSL could also promote the migration and invasion of H460 cells. Moreover, C8-HSL promoted the proliferation, migration, and invasion of H460 cells by activating the PI3K/AKT/ERK pathway. C8-HSL promoted the cell cycle progression of H460 cells by upregulating the expression levels of CDC25A, c-MYC, p-GSK3β, p-Rb, and Cyclin E1, while downregulating the expression levels of p16 and p27. C8-HSL promoted the migration and invasion of H460 cells by upregulating the expression level of MMP9 and downregulating the expression level of E-cadherin. This is the first report of C8-HSL as a promoter of lung cancer cell proliferation, migration, and invasion. Taken together, C8-HSL is a potential risk factor for lung cancer, and strategies targeting C8-HSL-producing bacteria and monitoring C8-HSL concentrations may be beneficial for the prevention and control of lung cancer.