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

Arch Biochem Biophys. 2022 Sep 30:727:109346. doi: 10.1016/j.abb.2022.109346. Epub 2022 Jul 5.

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.

Keywords: Breast cancer; Interferon; NFIC1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / pathology
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferons / genetics
  • Interferons / metabolism
  • Interferons / pharmacology
  • Janus Kinases* / metabolism
  • Melanoma
  • Melanoma, Cutaneous Malignant
  • NFI Transcription Factors / metabolism*
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Skin Neoplasms

Substances

  • NFI Transcription Factors
  • NFIC protein, human
  • STAT Transcription Factors
  • Interferons
  • Janus Kinases