Scholarlink

Background <p>Transcription factors (TFs) act together with co-regulators to modulate the expression of their target genes, which eventually dictates their pathophysiological effects. Depending on the co-regulator, TFs can exert different activities. The Estrogen Related Receptor α (ERRα) acts as a transcription factor that regulates several pathophysiological phenomena. In particular, interactions with PGC-1 co-activators are responsible for the metabolic activities of ERRα. In breast cancers however, ERRα exerts several tumor-promoting, metabolism-unrelated activities that do not depend on PGC-1, questioning the identity of the co-activators involved in these cancer-related effects.</p> Methods <p>Bio-computing methods were used to identify a potential ERRα coactivating factor in aggressive breast cancers. Bench experiments (qPCR, ChIP, proximity ligation assays) were used to validate the effect of the co-factor on ERRα transcriptional activity specifically in triple negative breast cancer (TNBC) cells. Predictive value of ERRα-co-factor target genes on the survival of TNBC patients was studied.</p> Results <p>ZEB1 appears as a major ERRα co-factor, involved in increased expression of direct ERRα targets that induce cell migration in TNBCs. Experimental validations establish that ERRα and ZEB1 interact together and are bound to the promoters of the target genes that they transcriptionally coregulate. Further analyses show that the ERRα-ZEB1 downstream transcriptional signature can predict the survival of TNBC patients.</p> Conclusions <p>Our approach combining bio-computing as well as experimental validation allows to propose a gene signature, the high expression of which predicts TNBC patient survival. Down modulation of these genes could be promising against TNBCs.</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

An ERRα-ZEB1 transcriptional signature predicts survival in triple-negative breast cancers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月8日

查看全文
  • Jing-Ru Shi,
  • Coralie Poulard,
  • Catherine Cerutti,
  • Olivier Trédan,
  • Muriel Le Romancer,
  • Tie-Liu Shi,
  • Jean-Marc Vanacker

摘要

Background

Transcription factors (TFs) act together with co-regulators to modulate the expression of their target genes, which eventually dictates their pathophysiological effects. Depending on the co-regulator, TFs can exert different activities. The Estrogen Related Receptor α (ERRα) acts as a transcription factor that regulates several pathophysiological phenomena. In particular, interactions with PGC-1 co-activators are responsible for the metabolic activities of ERRα. In breast cancers however, ERRα exerts several tumor-promoting, metabolism-unrelated activities that do not depend on PGC-1, questioning the identity of the co-activators involved in these cancer-related effects.

Methods

Bio-computing methods were used to identify a potential ERRα coactivating factor in aggressive breast cancers. Bench experiments (qPCR, ChIP, proximity ligation assays) were used to validate the effect of the co-factor on ERRα transcriptional activity specifically in triple negative breast cancer (TNBC) cells. Predictive value of ERRα-co-factor target genes on the survival of TNBC patients was studied.

Results

ZEB1 appears as a major ERRα co-factor, involved in increased expression of direct ERRα targets that induce cell migration in TNBCs. Experimental validations establish that ERRα and ZEB1 interact together and are bound to the promoters of the target genes that they transcriptionally coregulate. Further analyses show that the ERRα-ZEB1 downstream transcriptional signature can predict the survival of TNBC patients.

Conclusions

Our approach combining bio-computing as well as experimental validation allows to propose a gene signature, the high expression of which predicts TNBC patient survival. Down modulation of these genes could be promising against TNBCs.