Related Experiment Video

Updated: Sep 22, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.1K

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
PubMed

Insights

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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