PPDPF Promotes The Invasion And Metastasis Of Non-small Cell Lung Cancer Via Activating TGF-β Signaling

Background & Aim:Invasion and metastasis lead to the poor prognosis of non-small cell lung cancer(NSCLC).Identifying new targets affecting invasion and metastasis may shed light into the treatment of NSCLC.PPDPF is overexpressed in the lung cancer and promotes the radio-resistance of lung cancer cells as we previously reported,while its role in the invasion and metastasis of lung cancer remains elusive.In this study,we explored the underlying mechanisms and the functions of PPDPF in the metastasis of NSCLC and the underlying mechanisms.Method:Wound healing and transwell assay were used to evaluate the migration and invasion capacity of NSCLC cells.The interaction of PPDPF and TGF-βRII was verified by Immunoprecipitation(IP).The level of phosphorylated Smad2(p-Smad2)were detected by Western blot.The expression level of CTGF was analyzed by real-time PCR.The expression level of PPDPF and PGAM1 in NSCLC samples were analyzed by real-time PCR.Kaplan Meier Plotter database was used to analyze the correlation between the overall survival and the expression of PPDPF and PGAM1.The expression of PGAM1 in response to TGF-β1treatment was detected by Western blot.Results:PPDPF promotes the migration and invasion of NSCLC in vitro as well as the metastasis in vivo.Mechanistically,PPDPF interacts with TGF-βRII,and promotes the metastasis of NSCLC via enhancing TGF-βsignaling.PPDPF expression is upregulated in NSCLC clinical samples and predicts poor prognosis.Moreover,PGAM1 is a target gene of PPDPF/TGF-β signaling.Conclusions:PPDPF promotes the invasion and metastasis of NSCLC by upregulating the expression of PGAM1 via TGF-β signaling pathway,suggesting that PPDPF and PGAM1 are promising targets for the treatment of NSCLC.