NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway

NFIC1, the longest isoform of NFIC, is essential for the regulation on spatiotemporal expressions of drug-metabolizing genes in liver. However, the role of NFIC1 in breast cancer is not clear. Here we showed that increased expression of NFIC1 suppressed the migration and invasion of MCF-7 cells. The activation of interferon-associated Jak-STAT pathway was enhanced with NFIC1 overexpression. NFIC1 overexpression upregulated the expression of IFNB1, IFNL1, IFNL2 and IFNL3. Treatment with Jak-STAT pathway inhibitors, Filgotinib or Ruxolitinib, reversed the suppressive effects of NFIC1 overexpression on migration and invasion. In addition, we found that MX1 and MX2 were the target genes of NFIC1- activated Jak-STAT pathway, which mediated the migration and invasion of MCF-7 cells. These results demonstrated that NFIC1 inhibited the migration and invasion in MCF-7 cells through interferon mediated activation of Jak-STAT pathway, indicating that Jak-STAT pathway might be a potential therapeutic target for preventing breast cancer metastasis. Overall design: Total RNA obtained from MCF7 cells transiently transfected with pcDNA3.1 (Control) or pcDNA3.1-NFIC1 (NFIC1).