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Upregulation of transforming growth factor-beta type I receptor by interferon consensus sequence-binding protein in

Jee Young Sung1, Kyungsil Yoon2, Sang-Kyu Ye3

  • 1Rare Cancer Branch, Division of Clinical Research, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea.

Biochimica Et Biophysica Acta. Molecular Cell Research
|February 3, 2019
PubMed

Insights

Interferon consensus sequence-binding protein (ICSBP) promotes osteosarcoma progression by upregulating TGF-β RI. ICSBP binds to the TGF-β RI promoter, increasing tumor cell growth and tumorigenicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Transforming growth factor-beta (TGF-β) has dual roles in cancer, acting as a suppressor early on and a promoter later.
  • Interferon consensus sequence-binding protein (ICSBP), also known as interferon regulatory factor-8, shows a positive correlation with TGF-β type I receptor (TGF-β RI) in osteosarcoma.

Purpose of the Study:

  • To investigate the role of ICSBP in osteosarcoma progression.
  • To elucidate the mechanism by which ICSBP influences TGF-β RI expression and tumorigenicity.

Main Methods:

  • Osteosarcoma cell line experiments including soft agar growth assays and xenograft mouse models.
  • TGF-β RI promoter assays, electro mobility shift assays, and chromatin immunoprecipitation assays.
  • Analysis of ICSBP and TGF-β RI expression correlation in tumor types using cBioportal database.

Main Results:

  • ICSBP overexpression upregulated TGF-β RI and induced epithelial-to-mesenchymal transition-like phenomena in osteosarcoma cells.
  • ICSBP increased osteosarcoma cell tumorigenicity, which was reversible by ICSBP knockdown or TGF-β RI inhibition.
  • ICSBP directly binds to a specific site (nucleotides -216/-211) in the TGF-β RI promoter, activating its expression.

Conclusions:

  • ICSBP promotes osteosarcoma progression by upregulating TGF-β RI expression through direct promoter binding.
  • Targeting the ICSBP-TGF-β RI axis may offer a therapeutic strategy for osteosarcoma.
  • A positive correlation between ICSBP and TGF-β RI expression exists in multiple tumor types.
Keywords:
Interferon consensus sequence-binding proteinOsteosarcoma progressionPromoter activationTransforming growth factor-beta type I receptor

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