Helicobacter pylori (H. pylori)
infection is the strongest risk factor for the occurrence and development of gastric
carcinoma. However, the molecular mechanism underlying H. pylori-induced pathogenesis has not yet been fully characterized. Here, we explored whether H. pylori upregulates
semaphorin 5A to promote
gastric cancer progression via the extracellular regulated
protein kinases/
matrix metalloproteinase (ERK/MMP9) signaling pathway. In this study, H. pylori upregulated
semaphorin 5A expression in vitro and in vivo. Using the human gastric
carcinoma cell lines SGC7901, SGC7901-siScrambled, and SGC7901-siSema 5A, our studies showed that H. pylori increased the proliferation, growth, migration, and invasiveness of
gastric cancer cells via its effects on
semaphorin 5A and that H. pylori increased the expression of MMP9 in
gastric cancer cells via the
semaphorin 5A-mediated ERK signaling pathway. Further analysis revealed that the ERK inhibitor
PD98059 and MMP9 antibody (Ab) attenuated H. pylori-induced
gastric cancer cell invasion and
metastasis in vitro through a
semaphorin 5A-dependent mechanism. In conclusion, H. pylori could promote
gastric cancer progression in a
semaphorin 5A-dependent manner via the ERK/MMP9 signaling pathway.
Semaphorin 5A and its related signaling molecules potentially represent latent targets for H. pylori-related
gastric cancer therapy.