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Published on: July 20, 2019
NFIC1 suppresses migration and invasion of breast cancer cells through interferon-mediated Jak-STAT pathway
Jing Zhang1, Mingyue Fan1, Chanjuan Jin2
1China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, 130033, China; School of Life Sciences, Jilin University, Changchun, Jilin, 130012, China.
Abstract:
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.
Insights
NFIC1 suppresses breast cancer cell migration and invasion by activating the interferon-mediated Jak-STAT pathway. This pathway, involving genes like MX1 and MX2, offers a potential therapeutic target for preventing cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- NFIC1, the longest NFIC isoform, regulates drug-metabolizing genes in the liver.
- The role of NFIC1 in breast cancer progression remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of NFIC1 in breast cancer, specifically its effects on cell migration and invasion.
- To elucidate the molecular mechanisms underlying NFIC1's action in MCF-7 breast cancer cells.
Main Methods:
- Overexpression of NFIC1 in MCF-7 cells.
- Analysis of gene expression (IFNB1, IFNL1-3, MX1, MX2).
- Assessment of Jak-STAT pathway activation and inhibition using specific drugs (Filgotinib, Ruxolitinib).
Main Results:
- NFIC1 overexpression significantly suppressed MCF-7 cell migration and invasion.
- NFIC1 enhanced the expression of interferon genes (IFNB1, IFNL1-3) and activated the Jak-STAT pathway.
- Inhibition of the Jak-STAT pathway reversed the anti-migratory and anti-invasive effects of NFIC1.
- Jak-STAT target genes MX1 and MX2 were identified as mediators of cell migration and invasion.
Conclusions:
- NFIC1 inhibits breast cancer cell migration and invasion via the interferon-mediated Jak-STAT pathway.
- The Jak-STAT pathway, modulated by NFIC1, represents a potential therapeutic target for inhibiting breast cancer metastasis.
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