Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-018-06081-9
Title: Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression
Authors: Jiang Y. 
Jiang Y.-Y. 
Xie J.-J.
Mayakonda A. 
Hazawa M. 
Chen L.
Xiao J.-F. 
Li C.-Q.
Huang M.-L.
Ding L.-W. 
Sun Q.-Y. 
Xu L. 
Kanojia D. 
Jeitany M. 
Deng J.-W. 
Liao L.-D.
Soukiasian H.J.
Berman B.P.
Hao J.-J.
Xu L.-Y.
Li E.-M.
Wang M.-R.
Bi X.-G.
Lin D.-C. 
Koeffler H.P. 
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: Jiang Y., Jiang Y.-Y., Xie J.-J., Mayakonda A., Hazawa M., Chen L., Xiao J.-F., Li C.-Q., Huang M.-L., Ding L.-W., Sun Q.-Y., Xu L., Kanojia D., Jeitany M., Deng J.-W., Liao L.-D., Soukiasian H.J., Berman B.P., Hao J.-J., Xu L.-Y., Li E.-M., Wang M.-R., Bi X.-G., Lin D.-C., Koeffler H.P. (2018). Co-activation of super-enhancer-driven CCAT1 by TP63 and SOX2 promotes squamous cancer progression. Nature Communications 9 (1) : 3619. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-018-06081-9
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 co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically 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. © 2018, The Author(s).
Source Title: Nature Communications
URI: http://scholarbank.nus.edu.sg/handle/10635/152129
ISSN: 20411723
DOI: 10.1038/s41467-018-06081-9
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
s41467-018-06081-9.pdf3.51 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

20
checked on Oct 19, 2019

Page view(s)

41
checked on Oct 17, 2019

Download(s)

2
checked on Oct 17, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.