AIB1 and ANCO1 Regulate YAP/TEAD Signaling in Early Stage Basal Breast Cancer
Riegel, Anna T
The progression of ductal carcinoma in-situ (DCIS) to locally invasive breast cancer precedes distant metastases and disease lethality. The Amplified In Breast cancer 1 (AIB1) transcription coactivator becomes overexpressed and hyperactive during the transformation of normal mammary tumor to malignant disease and is critical to the transition of DCIS to invasive breast cancer. However, it is not known which factors mediate AIB1 effects in this context. Using gene expression analyses, ChIP-seq, and bioinformatic analyses, we found that AIB1 interaction with the YAP-TEAD complex is critical for coregulation of a subset of target genes in normal mammary cells and early stage breast cancer. AIB1-YAP transcription coactivation significantly enhances the expression of genes that drive aberrant growth of epithelial cells in 3D and in vivo. Conversely, we discovered that the ANCO1 tumor suppressor is recruited to YAP-TEAD by AIB1 to repress transcription of select genes. These corepressive patterns are distinct from AIB1-YAP coactivation, and, most notably, attenuate levels of S100A and SPRR genes, located at 1q21.3 locus. Loss of ANCO1 enhances YAP-driven invasive 3D sphere growth, in part through increases in individual cell size. In DCIS xenografts and breast cancer patient samples, loss of ANCO1 coincides with disease progression, thereby reverting AIB1-YAP repression. Our data demonstrates that transcription de-repression of 1q21.3 genes couples with hyperactive transcription of AIB1-YAP targets to promote progression of early stage breast cancer.
Showing items related by title, author, creator and subject.
Predictive Value of Estrogen Receptor Status as Assessed by Ligand-Binding Assay in Patients With Early-Stage Breast Cancer Treated With Breast Conserving Surgery and Radiation Therapy Takei, Hiroyuki; Horiguchi, Jun; Maemura, Michio; Koibuchi, Yukio; Oyama, Tetsunari; Yokoe, Takao; Iino, Yuichi; Morishita, Yasuo (2002-03)