NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
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NFIC1通过干扰素介导的Jak-STAT通路抑制乳腺癌细胞的迁移和侵袭
DOI：
10.1016/j.abb.2022.109346
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发表时间：
2022
影响因子：
3.9
通讯作者：
Youzhong Wan
中科院分区：
文献类型：
--
作者：
Jing Zhang;Mingyue Fan;Chanjuan Jin;Zhaoying Wang;Yutong Yao;Yueru Shi;Xin Hu;Youzhong Wan
NFIC 1是NFIC最长的亚型，对肝脏药物代谢基因的时空表达调控至关重要。然而，NFIC 1在乳腺癌中的作用尚不清楚。在这里，我们发现NFIC 1表达的增加抑制了MCF-7细胞的迁移和侵袭。NFIC 1过表达增加了IFN B1、IFN L1、IFN L2和IFN L3的表达，并且NFIC 1过表达增强了干扰素介导的Jak-STAT通路的激活。用Jak-STAT通路抑制剂Filgotinib或Ruxolitinib治疗，逆转了NFIC 1过表达对MCF-7细胞迁移和侵袭的抑制作用。另外，我们发现Jak-STAT信号通路的两个靶基因MX 1和MX2介导了MCF-7细胞的迁移和侵袭。这些结果表明NFIC 1通过干扰素介导的Jak-STAT通路的激活抑制MCF-7细胞的迁移和侵袭，提示Jak-STAT通路可能是预防乳腺癌转移的潜在治疗靶点。
NFIC1, the longest isoform of NFIC, is essential for the regulation on spatiotemporal expression 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. NFIC1 overexpression increased the expression of IFNB1, IFNL1, IFNL2 and IFNL3, and the activation of interferon-mediated Jak-STAT pathway was enhanced by NFIC1 overexpression. Treatment with Jak-STAT pathway inhibitors, Filgotinib or Ruxolitinib, reversed the suppressive effects of NFIC1 overexpression on migration and invasion of MCF-7 cells. In addition, we found that MX1 and MX2, two target genes of Jak-STAT pathway, 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.