Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop.
Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop.
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Hippo 信号通过 Yki-Src42A 正反馈环抑制肿瘤细胞转移
DOI：
10.1038/s41419-021-04423-y
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发表时间：
2021-12-03
影响因子：
9
通讯作者：
Zhou Z
中科院分区：
文献类型：
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作者：
Ding Y;Wang G;Zhan M;Sun X;Deng Y;Zhao Y;Liu B;Liu Q;Wu S;Zhou Z
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.
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