A Research On The Role Of DDR1 On Lung Metastasis Of Hepatocellular Carcinoma And Its Potential Molecular Mechanism

The long-term prognosis of patients with hepatocellular carcinoma is poor.Higher recurrence rate and metastasis rate are important reasons for poor prognosis of patients with hepatocellular carcinoma.Therefore,further study on the molecular mechanism of recurrence and metastasis of hepatocellular carcinoma is necessary.DDR1 is a novel member of the receptor tyrosine kinase family,and its ligand is collagen.DDR1 is highly expressed in many tumors.However,its role in lung metastasis of hepatocellular carcinoma and its specific molecular mechanism need to be further studied.In our study,we found that overexpression of DDR1 could promote the migration,invasion and lung metastasis of hepatocellular carcinoma cells through DDR1/PSD4/ARF6 signaling pathway.Firstly,the expression level of DDR1 in TNM stage II-IV was higher than that in TNM stage I in hepatocellular carcinoma.DDR1 promoted the migration,invasion and lung metastasis of hepatocellular carcinoma cells in vivo and in vitro.Mechanically,DDR1 interacted with ARF6 and promoted the activation of ARF6.To further explore the mechanism,we found that DDR1 recruited PSD4 to ARF6,which led the activation of ARF6 and its downstream MAPK signaling pathway.Our results revealed that the DDR1/PSD4/ARF6 signaling pathway was an important molecular mechanism in regulation of the migration,invasion and lung metastasis of hepatocellular carcinoma cells.Finally,we concluded that DDR1 played a role in lung metastasis of HCC and DDR1 may serve as a novel prognostic biomarker and a therapeutic strategy for hepatocellular carcinoma.