PRIM1 enhances colorectal cancer liver metastasis via promoting neutrophil recruitment and formation of neutrophil extracellular trap

Despite advances in treatment, liver metastasis remains the predominant pattern of distant spread for colorectal cancer (CRC) and a major cause of cancer-related mortality. DNA Primase Subunit 1 (PRIM1) has been reported to play important roles in cancer progression. This study investigated the role of PRIM1 in CRC liver metastasis, focusing on its influence on neutrophil recruitment and the formation of neutrophil extracellular traps (NETs). In this study, PRIM1 was upregulated in liver metastasis tumor tissues. CCK-8 and Transwell assays showed that the proliferation, migration and invasion of CRC cells were promoted with the ablation of PRIM1 and inhibited with PRIM1 overexpression. For in vivo investigation, we observed that PRIM1 ablation reduced the number and size of metastasis nodules of MC38 cells. Importantly, PRIM1 depletion obviously reduced the percentage of Ly6G+ neutrophils in liver. In contrast, overexpression of PRIM1 reversed these effects. Besides, depletion of neutrophils by anti-Ly6G antibody in mice notably attenuated liver metastasis burden induced by the upregulation of PRIM1. Western blot and immunohistochemistry assays revealed that three chemokines CXCL8, C-GSF and CXCL2 were confirmed to be upregulated with PRIM1 overexpression. Furthermore, PRIM1 overexpression reduced the formation of NETs. These results suggested that PRIM1 could facilitate the liver metastasis of CRC via recruiting neutrophils and NET formation. In conclusion, our novel findings highlighted the important role of PRIM1 in neutrophil recruitment and CRC metastasis and provided new perspectives and potential targets for future research and treatment for CRC.