GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE80372 Query DataSets for GSE80372
Status Public on Jun 16, 2016
Title A splicing switch of TEAD4 regulates Hippo-YAP signaling pathway to inhibit tumor proliferation
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Splicing dysregulations extensively occur in cancers, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signaling, a key pathway that regulates cell proliferation and organ size, is under control of a new splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signaling, undergoes alternative splicing facilitated by the tumor suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks N-terminal DNA-binding domain but maintains YAP-interaction domain. TEAD4-S is located in both nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumor growth in xenograft mouse model. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether these data reveal a novel RBM4-mediated splicing switch that serves to fine-tune Hippo-YAP pathway.
Overall design Cell lines stably expressing YAP, YAP/TEAD4-S, YAP/TEAD4-FL, YAP/RBM4 and control vector were created, and the total RNA was purified from the cells using TRIzol reagents. The polyadenylated RNAs were purified for construction of sequencing library using kapa TruSeq Total RNA Sample Prep kits (UNC High Throughput Sequencing Facility).
Contributor(s) Qi Y, Yu J, Han W, Wang Y, Wang Z
Citation(s) 27291620
Submission date Apr 18, 2016
Last update date May 15, 2019
Contact name Zefeng Wang
Organization name CAS-MPG Partner Institute for Computational Biology (PICB)
Street address 320 Yueyang Road
City Shanghai
ZIP/Postal code 200031
Country China
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (5)
GSM2125378 pCDNA-ctl
GSM2125379 YAP
GSM2125380 YAP-TEAD434
BioProject PRJNA318757
SRA SRP073434

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE80372_genes-merge.counts.matrix.gz 274.4 Kb (ftp)(http) MATRIX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap