Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop

Autor: Yan Ding, Guiping Wang, Meixiao Zhan, Xiaohan Sun, Yanran Deng, Yunhe Zhao, Bin Liu, Qingxin Liu, Shian Wu, Zizhang Zhou
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-021-04423-y
Popis: 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.
Databáze: Directory of Open Access Journals