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CTCF and EGR1 suppress breast cancer cell migration through transcriptional control of Nm23-H1

Ka Ming Wong1, Jiaxing Song1, Yung H Wong2,3

  • 1Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.

Scientific Reports
|January 13, 2021
PubMed

Insights

Tumor metastasis, a major cancer challenge, is linked to Nm23-H1 protein levels. This study reveals that transcription factors CTCF and EGR1 regulate Nm23-H1 expression in breast cancer cells, impacting metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor metastasis is a primary cause of cancer mortality.
  • Nm23-H1 is a known metastasis suppressor protein, but its regulatory mechanisms are unclear.
  • Loss of Nm23-H1 correlates with increased metastatic potential in aggressive cancers.

Purpose of the Study:

  • To investigate the mechanisms controlling Nm23-H1 expression in breast cancer cells.
  • To identify transcription factors involved in Nm23-H1 regulation.
  • To understand the role of Nm23-H1 regulation in breast cancer cell invasiveness.

Main Methods:

  • Comparative analysis of Nm23-H1 expression in MDA-MB-231 (low Nm23-H1) and MCF-7 (high Nm23-H1) breast cancer cells.
  • Promoter truncational analysis to identify regulatory regions.
  • Investigation of transcription factor binding (CTCF, EGR1) and their effect on Nm23-H1 expression and cell migration.

Main Results:

  • Nm23-H1 mRNA and protein levels correlated in breast cancer cell lines, suggesting transcriptional control.
  • A proximal promoter region with binding sites for CTCF and EGR1 was identified.
  • CTCF and EGR1 induced Nm23-H1 expression and reduced cell migration in MDA-MB-231 cells.
  • CTCF and EGR1 were recruited to the Nm23-H1 promoter in MCF-7 cells, correlating with Nm23-H1 levels.

Conclusions:

  • Downregulation of CTCF and EGR1 likely contributes to the loss of Nm23-H1 in aggressive breast cancer.
  • CTCF and EGR1 play a crucial role in driving Nm23-H1 expression.
  • Restoring CTCF and EGR1 expression may promote a less invasive phenotype in breast cancer.

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