OR30-3 Direct and VGLL1-Mediated Gene Regulation by GRHL2 During Mesenchymal to Epithelial Transition in Breast Cancer

Abstract The transcription factor (TF) GRHL2 controls normal epithelial differentiation in different tissues. It is expressed all breast cancer subtypes except those with a mesenchymal phenotype (claudin-low subtype), where its ectopic expression leads to induction of mesenchymal-epithelial transition (MET) (1). Here we explored the mechanisms by which induces MET claudin-low cell lines using combination ChIP-seq and RNAseq analyses upon modulation lines. Direct DNA binding was enriched proximity genes positively regulated lines, include several TFs as well an array genes. Biotinylation mass spectrometry analysis membrane proteins confirmed surfaceome remodeling via roles cell-cell contacts adhesion. Repression mediated part direct miRNAs targeting factors. In addition, strongly induced cofactor VGLL1, whose high triple-negative (TNBC) basal-like subtype. VGLL1 overexpression suppression TNBC cells role mediating signaling, particular interaction TEAD also interacted cells, recruiting it some motifs, suggesting multilayered cross-talk between Together, our results indicate that acts master regulator upregulation factors, resulting both genes.(1) Cieply B. et al., Cancer Res. 2013 Oct. 1;73 (20): 6299-309 Presentation: Tuesday, June 14, 2022 10:15 a.m. - 10:30