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.

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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