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Updated: Sep 22, 2025
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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The Hippo pathway mediates Semaphorin signaling
Zhipeng Meng1,2,3, Fu-Long Li1, Cao Fang1
1Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Science Advances
|May 25, 2022
Summary
Class 3 Semaphorins (SEMA3s) activate the Hippo pathway to inhibit tissue growth, angiogenesis, and tumor formation. This discovery reveals a new mechanism for SEMA3s in regulating biological processes.
Area of Science:
- Cell biology
- Molecular biology
- Cancer research
Background:
- Semaphorins are known for axonal guidance but also influence vascular development and tumorigenesis.
- The precise signaling pathways of Semaphorins in these processes are not fully understood.
Purpose of the Study:
- To investigate the downstream signaling cascades of Semaphorins, specifically Class 3 Semaphorins (SEMA3s).
- To determine the role of SEMA3s in regulating tissue growth, angiogenesis, and tumorigenesis through the Hippo pathway.
Main Methods:
- Investigated SEMA3B restoration in lung cancer cells.
- Analyzed the interaction between SEMA3A receptor PlexinA and p190RhoGAPs.
- Studied the activation of Hippo kinases LATS1/2.
Main Results:
- Class 3 Semaphorins (SEMA3s) activate the Hippo pathway to suppress tissue growth, angiogenesis, and tumorigenesis.
- SEMA3B restoration inhibited lung cancer cell growth by activating LATS1/2.
- SEMA3s inhibit angiogenesis via LATS1/2 activation.
- p190RhoGAPs act as key partners for PlexinA in Hippo pathway regulation.
- SEMA3 signaling activates p190RhoGAP, leading to LATS1/2 stimulation.
Conclusions:
- Class 3 Semaphorins (SEMA3s) utilize the Hippo pathway to control fundamental biological processes.
- The SEMA3-PlexinA-p190RhoGAP axis is critical for Hippo pathway activation.
- Disease-associated factors can disrupt SEMA3-mediated Hippo pathway regulation.
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