Streptococcus Pneumoniae Promotes Lung Tumorigenesis by Activating PI3K/AKT and NF-kB Pathways via Binding PspC to PAFR

Abstract

Streptococcus pneumoniae (SP) is associated with lung cancer, yet its role in the tumorigenesis remains uncertain. Herein we find that SP attaches to lung cancer cells via binding pneumococcal surface protein C (PspC) to platelet-activating factor receptor (PAFR), a receptor overexpressed in lung tumors. Interaction between PspC and PAFR stimulates cell proliferation and activates PI3K/AKT and NF-kB signaling pathways, which triggers a pro-inflammatory response. Lung cancer cells infected with SP rapidly form larger tumors in BALB/C mice compared to untreated cells. Mice treated with tobacco carcinogen and SP develop more lung tumors and had shorter survival than mice treated with the carcinogen alone. Mutating PspC or deleting PAFR abolishes the tumor-promoting effects of SP. Overabundance of SP is found in lung tumors of patients with lung cancer and associated with the survival. SP plays a driving role in lung tumorigenesis by activating PI3K/AKT and NF-kB pathways via binding PspC to PAFR and provides a microbial target for diagnosis and treatment of the disease.