Scholarlink

Background <p>Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are crucial during metastasis and therapy resistance. While the dynamics and master regulators of EMT are well-studied, the transcription factors that can prevent EMT or promote MET are relatively less understood.</p> Results <p>Here, by integrating bulk and spatial transcriptomic data analysis from cell lines and patient samples with mechanism-based dynamical modelling we identify IRF6 as a factor that strongly associates with an epithelial phenotype and is often inhibited during EMT. In vitro experiments in multiple cancer cell lines demonstrate the progression to a mesenchymal phenotype upon IRF6 knockdown, suggesting a role as an inhibitor of EMT. Finally, we observe that IRF6 expression levels correlate with worse patient survival in a subset of solid tumour types.</p> Conclusion <p>Our integrated computational-experimental, systems-level analysis suggests that IRF6 is frequently downregulated during EMT and can also prevent the progression towards a complete EMT, underscoring its role as an MET stabilizing factor.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Systems-level analysis identifies IRF6 as an inhibitor of epithelial-mesenchymal transition

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月14日

查看全文
  • Ayalur Raghu Subbalakshmi,
  • Aditya Agrawal,
  • Shibjyoti Debnath,
  • Kishore Hari,
  • Sarthak Sahoo,
  • Jason A. Somarelli,
  • Mohit Kumar Jolly

摘要

Background

Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are crucial during metastasis and therapy resistance. While the dynamics and master regulators of EMT are well-studied, the transcription factors that can prevent EMT or promote MET are relatively less understood.

Results

Here, by integrating bulk and spatial transcriptomic data analysis from cell lines and patient samples with mechanism-based dynamical modelling we identify IRF6 as a factor that strongly associates with an epithelial phenotype and is often inhibited during EMT. In vitro experiments in multiple cancer cell lines demonstrate the progression to a mesenchymal phenotype upon IRF6 knockdown, suggesting a role as an inhibitor of EMT. Finally, we observe that IRF6 expression levels correlate with worse patient survival in a subset of solid tumour types.

Conclusion

Our integrated computational-experimental, systems-level analysis suggests that IRF6 is frequently downregulated during EMT and can also prevent the progression towards a complete EMT, underscoring its role as an MET stabilizing factor.