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Novel role of the SOX4/CSNK2A1 axis in regulating TOP2A phosphorylation in breast cancer progression

Jiaqiong Zou1,2, Ruiman Geng1, Zhengkun Zhang1

  • 1Department of Biochemistry & Molecular Biology, West China School of Basic Sciences & Forensic Medicine, Sichuan University, Chengdu, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 11, 2025
PubMed

Insights

The SOX4/CSNK2A1 axis promotes breast cancer progression by increasing DNA topoisomerase II alpha (TOP2A) phosphorylation. Targeting this axis may offer new therapeutic strategies for breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer progression is complex and influenced by various molecular pathways.
  • DNA topoisomerase II alpha (TOP2A) phosphorylation plays a role in cancer development.
  • Understanding regulatory mechanisms is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate the role of the SRY-box transcription factor 4 (SOX4)/Casein kinase II subunit alpha 1 (CSNK2A1) axis in breast cancer.
  • To elucidate the mechanism by which SOX4/CSNK2A1 regulates TOP2A phosphorylation.
  • To explore the prognostic significance of immune profiles and the SOX4/CSNK2A1 axis in breast cancer.

Main Methods:

  • Integrated transcriptomic and proteomic analyses using CPTAC and TCGA data.
  • In vitro assays including RT-qPCR, Western blot, dual-luciferase reporter assays, and ChIP.
  • In vivo studies in mouse models and survival analysis of breast cancer patients.

Main Results:

  • Upregulation of SOX4 increases CSNK2A1 transcription, leading to enhanced TOP2A phosphorylation and accelerated breast cancer progression.
  • Three distinct immune profiles were identified, with an intermediate profile correlating with poorer prognosis due to SOX4/CSNK2A1-mediated TOP2A phosphorylation.
  • Silencing SOX4 reduced proliferation, migration, invasion, and tumor growth by decreasing CSNK2A1-TOP2A phosphorylation.

Conclusions:

  • The SOX4/CSNK2A1 axis is a key regulator of TOP2A phosphorylation in breast cancer.
  • Targeting the SOX4/CSNK2A1 axis presents a potential therapeutic strategy for breast cancer.
  • SOX4/CSNK2A1-mediated TOP2A phosphorylation influences breast cancer prognosis and immune profiles.
Keywords:
CSNK2A1 kinaseSOX4TOP2A phosphorylationbreast cancerproteomicstranscriptomicstumor growth and metastasis

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