S100A10 Promotes Pancreatic Ductal Adenocarcinoma Cells Proliferation, Migration and Adhesion through JNK/LAMB3-LAMC2 Axis

SIMPLE SUMMARY: Despite the advance in therapeutic strategy, the prognosis of pancreatic ductal adenocarcinoma (PDAC) is still unsatisfactory, with a 5-year survival rate of less than 9%. As a member of the S100 protein family, S100A10 has been identified as an oncogene in multiple cancers. In PDAC, S100A10 has been reported to be not only up-regulated in tumor tissues but also associated with survival outcomes. However, the specific function of S100A10 in PDAC is still unknown. Here, we suggest that S100A10 promotes PDAC cells proliferation, migration, and adhesion by activating JNK/LAMB3-LAMC2 axis in vitro and accelerates pancreatic tumor growth in vivo, indicating that S100A10 may be a potential therapeutic target for PDAC patients. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, characterized by diagnosis at an advanced stage and a poor prognosis. As a member of the S100 protein family, S100A10 regulates multiple biological functions related to cancer progression and metastasis. However, the role of S100A10 in PDAC is still not completely elucidated. In this study, we reported that S100A10 was significantly up-regulated in PDAC tissue and associated with a poor prognosis by integrated bioinformatic analysis and human PDAC tissue samples. In vitro, down-regulation of S100A10 reduced the proliferation, migration, and adhesion of PDAC cell lines, whereas up-regulation of S100A10 showed the opposite effect. Furthermore, LAMB3 was proved to be activated by S100A10 using RNA-sequencing and western blotting. The effect of LAMB3 on the proliferation, migration, and adhesion of PDAC cells was similar to that of S100A10. Up-regulation or down-regulation of LAMB3 could reverse the corresponding effect of S100A10. Moreover, we validated S100A10 activates LAMB3 through the JNK pathway, and LAMB3 was further proved to interact with LAMC2. Mice-bearing orthotopic pancreatic tumors showed that S100A10 knocked-down PANC-1 cells had a smaller tumor size than the control group. In conclusion, S100A10 promotes PDAC cells proliferation, migration, and adhesion through JNK/LAMB3-LAMC2 axis.