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Updated: Oct 15, 2025

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
11:28

Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics

Published on: May 11, 2016

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BRD4 Regulates Transcription Factor ΔNp63α to Drive a Cancer Stem Cell Phenotype in Squamous Cell Carcinomas

Matthew L Fisher1, Seamus Balinth1,2, Yon Hwangbo1

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.

Cancer Research
|October 26, 2021
PubMed

Insights

Bromodomain containing protein 4 (BRD4) drives aggressive cancer stem cell properties in squamous cell carcinomas by upregulating ΔNp63α. Targeting BRD4 inhibits tumor growth and metastasis, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cell Research

Background:

  • Cancer stem cells (CSCs) drive tumor recurrence and metastasis.
  • Bromodomain containing protein 4 (BRD4) is crucial for gene expression in development and cancer.
  • BRD4 inactivation shows promise as an anticancer therapy.

Purpose of the Study:

  • To investigate the role of BRD4 in cancer stem-like cells (CSCs) from squamous cell carcinomas (SCCs).
  • To identify the signaling pathways regulated by BRD4 in aggressive CSCs.
  • To evaluate BRD4 as a therapeutic target in SCC.

Main Methods:

  • Enrichment of CSC-like cells from SCC.
  • Analysis of stem cell marker expression, migration, and invasion.
  • Assessment of BRD4 and ΔNp63α levels.
  • Investigation of the BRD4-EZH2/STAT3-ΔNp63α signaling axis.
  • Inhibition of BRD4 in human SCC models.

Main Results:

  • CSCs enriched from SCC exhibit aggressive phenotypes and elevated BRD4.
  • BRD4 is critical for CSC-like properties, including migration, invasion, and tumor growth.
  • BRD4 regulates ΔNp63α expression via an EZH2/STAT3 complex.
  • Targeting BRD4 reduces ΔNp63α, inhibiting CSC-like properties and tumor growth in SCC.

Conclusions:

  • BRD4 is a key regulator of cancer stem-like cell properties in SCC.
  • A novel BRD4-driven signaling network involving ΔNp63α promotes aggressive CSC phenotypes.
  • Targeting BRD4 presents a potential therapeutic strategy for squamous cell carcinomas.

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