SOX4 reversibly induces phenotypic changes by suppressing the epithelial marker genes in human keratinocytes

Yoshiyuki Nagaoka1, Yukimasa Takeishi1, Yuki Miyake2

  • 1Department of Physiological Science and Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, Fukuoka, 814-0193, Japan.

Molecular Biology Reports
|January 16, 2024
PubMed
Abstract

Insights

SOX4, a transcription factor, reversibly induces an epithelial-to-mesenchymal transition (EMT)-like phenotype in human keratinocytes. This involves suppressing epithelial markers and promoting mesenchymal characteristics, offering insights into skin cell behavior.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Dermatology

Background:

  • SOX4 is a SOX (Sry-related High Mobility Group [HMG] box) family transcription factor crucial for biological processes.
  • SOX4 is present in adult skin and implicated in wound healing, tumor formation, and metastasis.

Purpose of the Study:

  • To investigate the role of SOX4 in keratinocyte phenotypic alterations.
  • To determine if SOX4 can induce an epithelial-to-mesenchymal transition (EMT)-like state in keratinocytes.

Main Methods:

  • Generated a doxycycline (DOX)-inducible SOX4-overexpressing keratinocyte cell line.
  • Utilized RNA sequencing for comprehensive gene expression analysis.
  • Confirmed gene and protein expression changes using qRT-PCR and Western blotting.

Main Results:

  • SOX4 overexpression induced a morphological shift from cobblestone to spindle-like keratinocytes.
  • RNA sequencing revealed decreased epithelial markers (e.g., KRT15, CLDN1) and increased mesenchymal markers (e.g., FN1).
  • SOX4's effects on epithelial and mesenchymal markers were reversible upon DOX removal.

Conclusions:

  • SOX4 reversibly induces an EMT-like phenotype in human keratinocytes.
  • This transition is mediated by the suppression of specific epithelial marker genes.
  • Findings contribute to understanding SOX4's role in skin biology and disease.

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