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Updated: Jan 20, 2026
07:16
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
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CCN1 interlinks integrin and hippo pathway to autoregulate tip cell activity
Myo-Hyeon Park1, Ae Kyung Kim1,2, Sarala Manandhar1
1BK21 Plus KNU Multi-Omics Creative Drug Research Team, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea.
Elife
|August 21, 2019
Summary
Cellular communication network factor 1 (CCN1) drives tumor angiogenesis by enhancing endothelial tip cell activity. Targeting CCN1, integrin αvβ3, and VEGFR2 may offer new therapies for pathological angiogenesis.
Area of Science:
- Oncology
- Vascular Biology
- Cell Signaling
Background:
- Cellular communication network factor 1 (CCN1/CYR61) is implicated in tumor angiogenesis, but its precise role and regulatory mechanisms remain unclear.
- Understanding CCN1's function is crucial for developing targeted therapies against pathological angiogenesis.
Purpose of the Study:
- To elucidate the mechanism by which CCN1 regulates endothelial tip cell activity in angiogenesis.
- To investigate the molecular pathways and interactions involved in CCN1-mediated angiogenesis.
Main Methods:
- Utilized CCN1-knockdown zebrafish embryos to observe microvessel network and cell migration.
- Investigated CCN1's effect on VEGFR2, MAPK/PI3K, YAP/TAZ, and mDia1 signaling pathways.
- Examined VEGFR2-integrin αvβ3 interaction via CCN1 in endothelial cell-specific Ccn1 transgenic mice and tumor models.
Main Results:
- CCN1 knockdown deformed microvessel networks and vascular cell migration in zebrafish embryos.
- CCN1 activated VEGFR2, MAPK/PI3K, YAP/TAZ, and mDia1, enhancing tip cell activity.
- VEGFR2-integrin αvβ3 interaction was mediated by CCN1, inhibiting tip cell proliferation and sprouting in mice models.
- High CCN1 expression in cancer patients correlated with poor survival and elevated ITGAV, ITGB3, and YAP/WWTR1 levels.
Conclusions:
- CCN1 positively regulates endothelial tip cell activity through a feedback loop involving integrin αvβ3, VEGFR2, and YAP/TAZ.
- This mechanism highlights CCN1 as a potential therapeutic target for pathological angiogenesis.
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