SHP1 Decreases the Level of P-STAT3(Ser727) and Inhibits Proliferation and Migration of Pancreatic Cancer Cells

PURPOSE To identify the direct effects and functional mechanisms of SHP1, plus its relationship with STAT3 in pancreatic cancer. METHODS Immunohistochemistry and Western blot assays were used to test SHP1 expression in pancreatic cancer. The functions of SHP1 in pancreatic cancer cells were analyzed by cell viability, colony formation, flow cytometric analysis of apoptosis, migration and invasion assays. Co-immunoprecipitation, combined with shotgun mass spectrometry, verified the direct or indirect interactions with JAK1 and p-STAT3(Ser727). Non-labeling and quantitative proteomics analysis evaluated the effect of SHP1 on protein expression levels. PRM phosphorylation modification of quantitative proteomics analysis confirmed p-STAT3(Ser727) levels. RESULTS SHP1 was missing or weakly expressed in human pancreatic ductal adenocarcinoma tissues and cells: PANC-1, AsPC-1, BxPC-3, and SW1990. SHP1 inhibited cell proliferation and migration. SHP1 had a slight effect on the protein expression level of PANC-1 cells. The level of p-STAT3(Ser727) was decreased by SHP1 at 0.53 multiple. Co-IP analysis revealed no direct or indirect interactions between SHP1and p-STAT3(Ser727) in protein complex patterns. CONCLUSION These results suggest that SHP1 negatively regulate pancreatic cancer cells progression. It inhibits STAT3 activation by decreasing STAT3 phosphorylation at serine 727.