RRC ID |
70771
|
著者 |
Ding Y, Wang G, Zhan M, Sun X, Deng Y, Zhao Y, Liu B, Liu Q, Wu S, Zhou Z.
|
タイトル |
Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop.
|
ジャーナル |
Cell Death Dis
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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.
|
巻・号 |
12(12)
|
ページ |
1126
|
公開日 |
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
|
リソース情報 |
ショウジョウバエ |
DGRC#102735
DGRC#109998
DGRC#108774 |