General Information
- Project ID
- OEP000074
- Project Name
- A splicing switch of TEAD4 regulates Hippo-YAP signaling pathway to inhibit tumor proliferation
- Description
- 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.
- Used ID
- NODEP00000038  
- Publications
-
A splicing isoform of TEAD4 attenuates the Hippo-YAP signalling to inhibit tumour proliferation.
Qi Y, Yu J, Han W, et al. A splicing isoform of TEAD4 attenuates the Hippo-YAP signalling to inhibit tumour proliferation[J]. Nature Communications, 2016, 7:ncomms11840.
(PMID: 27291620) (DOI: 10.1038/ncomms11840)
Project information
- Experiments
- 1
Experiment ID Experiment name Experiment type Create Date OEX000084 ZFWang_lab_NODEX00000037 Transcriptomic 2016-05-03 - Samples
- 1
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES001992 YAP-RBM4 Human Homo sapiens Lung Carcinom Cells 2016-05-03 - Runs
-
1
Run ID Run Name Experiment Sample Data Num Create Date OER008963 ZFWang_lab_NODER00000356 OEX000084 OES001992 5 2016-05-03
Author Information
- Create Date
- 2016-05-03
- Last Modified
- 2018-12-26
- Submission
- Xiaojuan Fan
- PICB