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

Yan Ding1, Guiping Wang2, Meixiao Zhan3

  • 1State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China.

Cell Death & Disease
|December 4, 2021
PubMed

Insights

The Hippo pathway normally stops tumor cell metastasis. Inhibiting this pathway activates YAP and SRC, creating a feedback loop that promotes cancer cell migration and offers a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Metastasis is a major cause of cancer mortality.
  • Understanding metastasis mechanisms is crucial for developing anti-cancer drugs.

Purpose of the Study:

  • To investigate the role of the Hippo pathway in tumor cell metastasis.
  • To identify molecular targets for anti-cancer therapies.

Main Methods:

  • In vivo studies of tumor cell metastasis.
  • Gene silencing (hpo, wts) and its effect on cell migration.
  • Analysis of transcriptional activation of src42A by Yki.
  • Investigating the YAP-SRC interaction in human hepatocellular carcinoma cells.

Main Results:

  • The Hippo pathway inhibits tumor cell metastasis.
  • Silencing hpo or wts promotes cell migration via Yki.
  • Hippo pathway inhibition upregulates src42A transcription through Yki.
  • A conserved Yki/YAP-Src42A/SRC positive feedback loop enhances cell migration.
  • SRC is a YAP target and promotes migration in human liver cancer cells.

Conclusions:

  • A conserved Yki/YAP-Src42A/SRC positive feedback loop drives tumor cell migration.
  • SRC is a potential therapeutic target for YAP-driven metastatic cancers.

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