Fig. 8: Scheme indicating the role of the ZEB1-ERα complex during early/hybrid EMT stages of breast cancer.
Non-invasive primary epithelial breast tumors (EpCAMhigh) that express high levels of ERα and are negative for ZEB1 expression are formed by the abnormal proliferation of luminal mammary epithelial cells. FOXA1 acts as the main pioneer factor for the recruitment of ERα for transcription of genes involved in cell proliferation. In early/hybrid states of EMT, AP2γ becomes a determining pioneer factor promoting the formation of a ZEB1-ERα complex at ERα binding sites, which enhances ERα target gene expression. Without AP2γ recruitment, FOXA1 and/or other factors may partially sustain ERα recruitment to ERBSs and ERα-stimulated transcription. This complex reprograms the ERα cistrome and transcriptome towards the activation of genes involved in partial EMT and metastatic dissemination. Expression of specific factors such as CD151 marks the partial EMT state. CD151 could potentially be targeted to prevent cancer cell proliferation, migration, and invasion. The illustration was created with BioRender.com.
