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Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
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SOX4 and SMARCA4 cooperatively regulate PI3k signaling through transcriptional activation of TGFBR2

Gaurav A Mehta1,2, Steven P Angus3, Christen A Khella1,2

  • 1Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

NPJ Breast Cancer
|April 10, 2021
PubMed

Insights

The transcription factor SOX4 regulates PI3K signaling in triple-negative breast cancer (TNBC). SOX4 and SMARCA4 form a complex essential for TNBC development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Dysregulated PI3K/Akt signaling is common in triple-negative breast cancer (TNBC).
  • Mechanisms controlling this pathway in TNBC are poorly understood.
  • SOX4 is a transcription factor implicated in various cancers.

Purpose of the Study:

  • To investigate the role of SOX4 in regulating PI3K signaling in TNBC.
  • To identify downstream targets and interacting proteins of SOX4 in TNBC.
  • To elucidate the molecular mechanisms underlying SOX4-mediated PI3K pathway activation in TNBC.

Main Methods:

  • Genomic and proteomic analyses were performed.
  • Mechanistic studies were conducted to understand gene regulation.
  • Chromatin conformation and protein complex formation were investigated.

Main Results:

  • SOX4 directly targets and upregulates TGFBR2 expression.
  • TGFBR2 mediates SOX4-dependent PI3K signaling.
  • SOX4 and SMARCA4 form a complex that maintains open chromatin at TGFBR2 regulatory regions, driving PI3K signaling.

Conclusions:

  • SOX4 and SMARCA4 cooperatively regulate PI3K/Akt signaling in TNBC.
  • This SOX4-SMARCA4 complex is crucial for TNBC initiation and progression.
  • Targeting this complex may offer a therapeutic strategy for TNBC.

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