| RRC ID |
70771
|
| Author |
Ding Y, Wang G, Zhan M, Sun X, Deng Y, Zhao Y, Liu B, Liu Q, Wu S, Zhou Z.
|
| Title |
Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop.
|
| Journal |
Cell Death Dis
|
| Abstract |
Metastasis is an important cause of death from malignant tumors. It is of great significance to explore the molecular mechanism of metastasis for the development of anti-cancer drugs. Here, we find that the Hippo pathway hampers tumor cell metastasis in vivo. Silence of hpo or its downstream wts promotes tumor cell migration in a Yki-dependent manner. Furthermore, we identify that inhibition of the Hippo pathway promotes tumor cell migration through transcriptional activating src42A, a Drosophila homolog of the SRC oncogene. Yki activates src42A transcription through direct binding its intron region. Intriguingly, Src42A further increases Yki transcriptional activity to form a positive feedback loop. Finally, we show that SRC is also a target of YAP and important for YAP to promote the migration of human hepatocellular carcinoma cells. Together, our findings uncover a conserved Yki/YAP-Src42A/SRC positive feedback loop promoting tumor cell migration and provide SRC as a potential therapeutic target for YAP-driven metastatic tumors.
|
| Volume |
12(12)
|
| Pages |
1126
|
| Published |
2021-12-3
|
| DOI |
10.1038/s41419-021-04423-y
|
| PII |
10.1038/s41419-021-04423-y
|
| PMID |
34862372
|
| PMC |
PMC8642408
|
| MeSH |
Animals
Drosophila / metabolism
Drosophila Proteins* / metabolism
Drosophila melanogaster / metabolism
Feedback
Hippo Signaling Pathway
Intracellular Signaling Peptides and Proteins / metabolism
Neoplasms* / genetics
Nuclear Proteins / metabolism
Protein Serine-Threonine Kinases / genetics
Proto-Oncogene Proteins pp60(c-src) / genetics
Proto-Oncogene Proteins pp60(c-src) / metabolism
Signal Transduction
Trans-Activators / metabolism
|
| IF |
6.304
|
| Resource |
| Drosophila |
DGRC#102735
DGRC#109998
DGRC#108774 |
