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Updated: Apr 18, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
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;
Abstract:
The Hippo and c-Jun N-terminal kinase (JNK) pathway both regulate growth and contribute to tumorigenesis when dysregulated. Whereas the Hippo pathway acts via the transcription coactivator Yki/YAP to regulate target gene expression, JNK signaling, triggered by various modulators including Rho GTPases, activates the transcription factors Jun and Fos. Here, we show that impaired Hippo signaling induces JNK activation through Rho1. Blocking Rho1-JNK signaling suppresses Yki-induced overgrowth in the wing disk, whereas ectopic Rho1 expression promotes tissue growth when apoptosis is prohibited. Furthermore, Yki directly regulates Rho1 transcription via the transcription factor Sd. Thus, our results have identified a novel molecular link between the Hippo and JNK pathways and implicated the essential role of the JNK pathway in Hippo signaling-related tumorigenesis.
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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