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CHD4 mediates SOX2 transcription through TRPS1 in luminal breast cancer

Jun Zhang1, Xiang Lv1, Bo Wei1

  • 1Department of Biochemistry, School of Life Sciences, Nanjing Normal University, Nanjing, China.

Cellular Signalling
|September 8, 2022
PubMed

Insights

Chromodomain helicase DNA binding protein 4 (CHD4) suppresses breast cancer stemness by repressing SOX2 expression. This regulation is mediated by CHD4 binding to the SOX2 promoter, influenced by TRPS1.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Chromodomain helicase DNA binding protein 4 (CHD4) is implicated in various cancers.
  • The role of CHD4 in breast cancer stemness remains largely unexplored.
  • Cancer stem cells (CSCs) drive tumor initiation and progression.

Purpose of the Study:

  • To investigate the role of CHD4 in regulating breast cancer stemness.
  • To elucidate the molecular mechanisms linking CHD4 to SOX2, a key CSC regulator.

Main Methods:

  • Analysis of CHD4's effect on SOX2 expression in breast cancer.
  • Chromatin immunoprecipitation (ChIP) assays to determine CHD4 binding to the SOX2 promoter.
  • Investigating the role of TRPS1 in mediating CHD4-SOX2 interaction.

Main Results:

  • CHD4 was found to repress SOX2 expression, thereby suppressing cancer stemness in breast cancer.
  • CHD4 directly binds to the promoter region of SOX2.
  • TRPS1 is essential for CHD4's transcriptional repression of SOX2.

Conclusions:

  • CHD4 acts as a suppressor of breast cancer stemness through the repression of SOX2.
  • The findings reveal a novel mechanism involving CHD4, TRPS1, and SOX2 in controlling CSC functions.
  • CHD4 is identified as a potential therapeutic target for overcoming breast cancer stemness.
Keywords:
Breast cancerCHD4SOX2Stemness

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