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Updated: Jun 7, 2026

Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model
Published on: November 13, 2012
Plexin B1 inhibits integrin-dependent pp125FAK and Rho activity in melanoma
Lindy McClelland1, Yulin Chen, Joanne Soong
1Department of Dermatology, University of Rochester School of Medicine, Rochester, NY, USA.
Abstract:
Semaphorins are secreted and membrane bound proteins that regulate axon guidance through receptors Plexins and neuropilins. Plexin B1, the Semaphorin 4D receptor, is a recently described tumor suppressor protein for melanoma. We recently showed that Plexin B1 abrogates activation of the oncogenic receptor, c-Met, by its ligand, hepatocyte growth factor (HGF), in melanoma. We have now investigated the effect of Plexin B1 on integrin-dependent pp125(FAK) activation, and the small GTP-binding protein Rho, in melanoma. Integrin receptors and Rho play critical roles in melanoma progression, through regulation of migration, proliferation and apoptosis. We engineered two human melanoma cell lines expressing Plexin B1 and analyzed integrin-dependent migration, integrin-dependent pp125(FAK) activation, and Rho activity. Results show that Plexin B1 abrogates integrin-dependent migration and activation of pp125(FAK). We also show that Rho activity is significantly reduced in cells expressing Plexin B1, and that Plexin B1 suppresses HGF-dependent Rho activation.
Insights
Plexin B1, a melanoma tumor suppressor, inhibits integrin-dependent cell migration and Rho activity. This protein also suppresses hepatocyte growth factor (HGF)-induced Rho activation in melanoma cells.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Semaphorins are proteins crucial for axon guidance, with Plexin B1 identified as a melanoma tumor suppressor.
- Plexin B1 has been shown to inhibit the oncogenic receptor c-Met signaling in melanoma.
- Integrin receptors and Rho GTPase are vital for melanoma progression, influencing migration, proliferation, and apoptosis.
Purpose of the Study:
- To investigate the effect of Plexin B1 on integrin-dependent focal adhesion kinase (pp125(FAK)) activation in melanoma.
- To determine the impact of Plexin B1 on Rho GTPase activity in melanoma cells.
- To elucidate the role of Plexin B1 in regulating melanoma cell migration and signaling pathways.
Main Methods:
- Engineered two human melanoma cell lines to stably express Plexin B1.
- Analyzed integrin-dependent cell migration using migration assays.
- Assessed integrin-dependent pp125(FAK) activation and Rho activity via biochemical assays.
- Investigated hepatocyte growth factor (HGF)-dependent Rho activation.
Main Results:
- Plexin B1 expression abrogated integrin-dependent melanoma cell migration.
- Activation of pp125(FAK) was significantly reduced in melanoma cells expressing Plexin B1.
- Rho activity was markedly decreased in Plexin B1-expressing cells.
- Plexin B1 suppressed HGF-induced Rho activation.
Conclusions:
- Plexin B1 acts as a suppressor of melanoma cell migration by inhibiting integrin-dependent pathways.
- Plexin B1 negatively regulates Rho GTPase activity, contributing to its tumor-suppressive function in melanoma.
- These findings highlight Plexin B1 as a potential therapeutic target for melanoma treatment by modulating key signaling pathways involved in metastasis.
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