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Updated: Jun 24, 2026
11:42
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function.
Yimin Wu1, Konstadinos Moissoglu, Hong Wang
1Department of Molecular Physiology, University of Virginia, Charlottesville, VA 22908, USA.
Summary
Rho-associated kinase GDI 2 (RhoGDI2) suppresses bladder cancer metastasis. Its function is enhanced by phosphorylation from Src kinase, suggesting caution with Src inhibitors in cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- RhoGDI2 is a known suppressor of metastasis in human bladder cancer.
- Diminished RhoGDI2 expression correlates with decreased patient survival, but its function can be regulated by other mechanisms.
Purpose of the Study:
- To investigate novel regulatory mechanisms of RhoGDI2 function in bladder cancer.
- To identify and characterize the interaction between RhoGDI2 and Src kinase.
Main Methods:
- Protein interaction analysis, gene expression profiling, and immunohistochemistry were used to identify Src as a RhoGDI2 partner.
- In vitro and in vivo studies confirmed Src kinase binding and phosphorylation of RhoGDI2.
- Site-directed mutagenesis identified key phosphorylation sites (Tyr-153 and Tyr-24).
Main Results:
- Src kinase binds and phosphorylates RhoGDI2, primarily at Tyr-153.
- Phosphorylation alters RhoGDI2 complex composition (reducing Rac1) and cellular localization (increasing membrane association).
- Expression of a phosphomimetic RhoGDI2 mutant suppressed metastasis more effectively than wild-type RhoGDI2.
Conclusions:
- Src-mediated phosphorylation enhances RhoGDI2's metastasis suppressive function in bladder cancer.
- Loss of Src kinase activity may relieve metastasis suppression in tumors expressing RhoGDI2.
- Targeting Src kinase inhibitors requires careful consideration due to potential effects on metastasis suppression.
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