2. Academic Validation
  3. 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

  • Cell Death Dis. 2021 Dec 3;12(12):1126. doi: 10.1038/s41419-021-04423-y.
Yan Ding  # 1,  Guiping Wang  # 2,  Meixiao Zhan  # 3,  Xiaohan Sun  # 1,  Yanran Deng 4,  Yunhe Zhao 1,  Bin Liu 1,  Qingxin Liu 5,  Shian Wu 6,  Zizhang Zhou 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China.
  • 2 Tianjin Key Laboratory of Protein Sciences, State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University, 300071, Tianjin, China.
  • 3 Center of Intervention radiology, Zhuhai Precision Medicine Center, Zhuhai People's Hospital, 519000, Zhuhai, China.
  • 4 Jiangsu Key laboratory of Drug Screening, China Pharmaceutical University, 210009, Nanjing, China.
  • 5 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China. liuqingxin@sdau.edu.cn.
  • 6 Tianjin Key Laboratory of Protein Sciences, State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University, 300071, Tianjin, China. wusa@nankai.edu.cn.
  • 7 State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China. zhouzz@sdau.edu.cn.
  • # Contributed equally.
PMID: 34862372 DOI: 10.1038/s41419-021-04423-y
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.

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