title: EphB3 Stimulates Cell Migration and Metastasis in a Kinase-dependent Manner through Vav2-Rho GTPase Axis in Papillary Thyroid Cancer.
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.
authors.affiliation: From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Sun
authors.affiliation: From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yuan
authors.affiliation: From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Yin
authors.affiliation: the Department of General Surgery, Fengxian Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, Shanghai 201499, China.
authors.forename: Yao-Gang
authors.initials: YG
authors.lastname: Bian
authors.affiliation: From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Long
authors.affiliation: the Department of General Surgery, Fengxian Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, Shanghai 201499, China lejing1996@aliyun.com.
authors.forename: Xue-Li
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: From the Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China and dxie@sibs.ac.cn.
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
mesh_terms: D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics / Q000378:metabolism*; D036223:Receptor, EphB3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C107953:RAC1 protein, human; C093651:VAV2 protein, human; D036223:Receptor, EphB3; D020830:rac1 GTP-Binding Protein
keywords: EphB3; Rho (Rho GTPase); Vav2; cancer biology; cell migration; focal adhesion; metastasis; papillary thyroid cancer