The Molecular Mechanism Of TM4SF1 In Pancreatic Cancer Cells Invasion And Metastasis By DDR1

Objective: We performed the research to detect the molecular mechanism of TM4SF1 on the invasion and metastasis of pancreatic cancer.To investigate that TM4SF1 promoted invasion and metastasis of pancreatic cancer cells by regulating DDR1 in PANC-1 and AsPC-1 cell lines.Methods: In PANC-1 and AsPC-1,we used double immuno-fluorescence and coimmunoprecipitation analyses to detect the interaction between TM4SF1 and DDR1.After silencing TM4SF1,the expression levels of DDR1 were detected using qRT-PCR and Western Blot.After DDR1 overexpressed,we investigated the migration and invasion abilities and the protein expression levels of MMP2 and MMP9.We used siTM4SF1 and plasma with DDR1 genes to investigate whether upregulating the expression levels of DDR1 rescued the inhibitory effects on migration and invasion and the protein expression levels of MMP2 and MMP9 after decreasing the expression levels of TM4SF1.Results: In PANC-1 and AsPC-1 cell lines,green DDR1 and red TM4SF1 colocalized the cell membrane.Also,co-IP assays showed an interaction between TM4SF1 and DDR1.After downregulating the expression of TM4SF1,the DDR1 mRNA and protein expression levels decreased significantly(P < 0.05).The results of Transwell and Western Blot analysis showed that the migrated and invaded cell numbers were increased and the protein expression levels of MMP2 and MMP9 were up-regulated after DDR1 overexpressed(P<0.05).After siRNA and plasmid transfected to cells,we found that increasing the expression levels of DDR1 rescuedthe inhibitory effects on migration and invasion and the protein expression levels of MMP2 and MMP9 after decreasing the expression levels of TM4SF1.Conclusion: In pancreatic cancer cells,TM4SF1 interacted with DDR1 and promoted the pancreatic cancer metastasis and invasion by regulating the expression levels of MMP2 and MMP9.