Impaired Hippo signaling promotes Rho1-JNK-dependent growth

Xianjue Ma1, Yujun Chen1, Wenyan Xu2

  • 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;

Insights

The Hippo pathway links to the JNK pathway via Rho1, revealing a new mechanism in cell growth regulation. This discovery is crucial for understanding Hippo signaling-related tumorigenesis.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Developmental biology

Background:

  • The Hippo and JNK pathways regulate cell growth and are implicated in cancer.
  • Hippo signaling functions through Yki/YAP, while JNK signaling involves Jun and Fos transcription factors.

Purpose of the Study:

  • To elucidate the molecular link between the Hippo and JNK pathways.
  • To investigate the role of JNK signaling in Hippo pathway-mediated tumorigenesis.

Main Methods:

  • Investigated Hippo signaling impairment and its effect on JNK activation.
  • Utilized genetic manipulation in Drosophila wing discs to study pathway interactions.
  • Analyzed transcriptional regulation of Rho1 by Yki and Sd.

Main Results:

  • Impaired Hippo signaling activates JNK signaling via Rho1.
  • Blocking Rho1-JNK signaling inhibits Yki-induced overgrowth.
  • Yki directly upregulates Rho1 transcription through the transcription factor Sd.

Conclusions:

  • A novel molecular connection between the Hippo and JNK pathways has been identified.
  • The JNK pathway plays a critical role in Hippo signaling-driven tumorigenesis.

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