We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression.
- Authors
Yuan Jiang; Yan-Yi Jiang; Jian-Jun Xie; Mayakonda, Anand; Hazawa, Masaharu; Li Chen; Jin-Fen Xiao; Chun-Quan Li; Mo-Li Huang; Ling-Wen Ding; Qiao-Yang Sun; Liang Xu; Kanojia, Deepika; Maya Jeitany; Jian-Wen Deng; Lian-Di Liao; Soukiasian, Harmik J.; Berman, Benjamin P.; Jia-Jie Hao; Li-Yan Xu
- Abstract
Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. However, functional consequence of their frequent colocalization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineagespecifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter. Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC-specific DNA/ RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and promotes SCC tumorigenesis, advancing our understanding of transcription dysregulation in cancer biology mediated by master TFs and super-enhancers.
- Publication
Nature Communications, 2018, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-06081-9