 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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 |
| E-mail(s) |
wangzefeng@picb.ac.cn
|
| 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)
|
|
| Relations |
| BioProject |
PRJNA318757 |
| SRA |
SRP073434 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE80372_genes-merge.counts.matrix.gz |
274.4 Kb |
(ftp)(http) |
MATRIX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...