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Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
EphB3 Stimulates Cell Migration and Metastasis in a Kinase-dependent Manner through Vav2-Rho GTPase Axis in Papillary
Jing-Jing Li1, Zhi-Jian Sun1, Yan-Mei Yuan1
1From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
Abstract:
Eph receptors, the largest subfamily of transmembrane tyrosine kinase receptors, have been increasingly implicated in various physiologic and pathologic processes, and the roles of the Eph family members during tumorigenesis have recently attracted growing attentions. In the present study, we explored the function of EphB3, one member of Eph family, in papillary thyroid cancer (PTC). We found that the expression of EphB3 was significantly elevated in PTC. Either overexpression of EphB3 or activation of EphB3 by EfnB1-Fc/EfnB2-Fc stimulated in vitro migration of PTC cells. In contrast, siRNA-mediated knockdown of EphB3 or EphB3-Fc treatment, which only blocked EphB3-mediated forward signaling, inhibited migration and metastasis of PTC cells. A mechanism study revealed that EphB3 knockdown led to suppressed activity of Rac1 and enhanced activity of RhoA. Moreover, we found that Vav2, an important regulator of Rho family GTPases, was activated by EphB3 in a kinase-dependent manner. Altogether, our work suggested that EphB3 acted as a tumor promoter in PTC by increasing the in vitro migration as well as the in vivo metastasis of PTC cells through regulating the activities of Vav2 and Rho GTPases in a kinase-dependent manner.
Insights
EphB3 receptor tyrosine kinase is elevated in papillary thyroid cancer (PTC), promoting cell migration and metastasis. Inhibiting EphB3 signaling suppressed tumor cell invasion by regulating Rac1 and RhoA GTPase activity.
Area of Science:
- Molecular Biology
- Oncology
- Cell Signaling
Background:
- Eph receptors are transmembrane tyrosine kinases involved in physiological and pathological processes.
- Their roles in tumorigenesis are gaining attention, particularly within the Eph family.
Purpose of the Study:
- To investigate the function of EphB3 in papillary thyroid cancer (PTC).
- To elucidate the underlying molecular mechanisms of EphB3's role in PTC progression.
Main Methods:
- Quantitative analysis of EphB3 expression in PTC tissues.
- In vitro cell migration assays using EphB3 overexpression and knockdown models.
- siRNA-mediated knockdown of EphB3.
- Analysis of Rho GTPase (Rac1, RhoA) and Vav2 activation.
- In vivo metastasis assays.
Main Results:
- EphB3 expression is significantly upregulated in PTC.
- EphB3 overexpression or activation enhances PTC cell migration in vitro.
- EphB3 knockdown or inhibition of forward signaling suppresses PTC cell migration and metastasis.
- EphB3 regulates Rac1 and RhoA activity and activates Vav2 in a kinase-dependent manner.
Conclusions:
- EphB3 acts as a tumor promoter in papillary thyroid cancer.
- EphB3 enhances PTC cell migration and metastasis via regulation of Vav2 and Rho GTPases.
- Targeting EphB3 signaling may represent a therapeutic strategy for PTC.
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Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...