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Hippo signaling promotes JNK-dependent cell migration.

Xianjue Ma1,2,3, Hongxiang Wang4, Jiansong Ji5

  • 1Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai 200092, China; xianjue.ma@yale.edu zxpkxy@126.com juxiangchen.cz@gmail.com lei.xue@tongji.edu.cn.

Proceedings of the National Academy of Sciences of the United States of America
|February 9, 2017
PubMed
Summary

Hippo pathway activation promotes cell invasion via JNK signaling, contrary to expectations. Targeting Yorkie or YAP may paradoxically increase cancer metastasis.

Keywords:
DrosophilaHippoJNKRox8migration

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Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Developmental Biology

Background:

  • Dysregulation of the Hippo pathway is linked to cancer progression, including cell proliferation, growth, and tumorigenesis.
  • The precise molecular mechanisms by which the Hippo pathway influences cell invasion remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying Hippo pathway-mediated cell invasion.
  • To investigate the role of JNK signaling and specific downstream components in this process.
  • To explore the implications for therapeutic strategies targeting the Hippo pathway in cancer.

Main Methods:

  • Utilized a *Drosophila* wing epithelium invasion model.
  • Investigated the role of JNK signaling in Hippo pathway activation-induced cell invasion.
  • Identified downstream effectors, including the *bantam*-Rox8 module.
  • Examined YAP and TIA1 expression and their impact on cell invasion in human cancer cells.

Main Results:

  • Activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition in *Drosophila* wing epithelium.
  • JNK signaling is crucial for Hippo pathway-induced matrix metalloproteinase 1 expression and cell invasion.
  • The *bantam*-Rox8 module acts downstream of Yorkie, mediating JNK-dependent cell invasion.
  • YAP negatively regulates TIA1 expression and cell invasion in human cancer cells.

Conclusions:

  • Hippo pathway activation drives cell invasion through JNK signaling and specific downstream targets.
  • Therapeutic strategies inhibiting Yorkie or YAP may inadvertently promote cancer cell invasion and metastasis.
  • These findings offer critical molecular insights into Hippo pathway-driven cancer progression and highlight potential therapeutic challenges.