RESUMO
EphB4 tyrosine kinase receptor has been involved in various physiologic and pathologic processes, and the role of the EphB4 in tumorigenesis has recently attracted much interest. However, its function in papillary thyroid carcinoma remains poorly understood. In this study, we explored the function of EphB4 in papillary thyroid carcinoma. We found that the expression of EphB4 was significantly upregulated in clinical samples. Overexpression of EphB4 in papillary thyroid carcinoma cell lines accelerated cell migration. In contrast, downregulation of EphB4 inhibited cell migration and suppressed in vivo tumor metastasis. Furthermore, we showed that EphB4 promoted cell migration by inhibiting the phosphorylation of FAK and paxillin. Moreover, EphB4 promoted cell migration in a kinase-independent manner. Taken together, our findings suggest that EphB4 plays an important role in the progression of papillary thyroid carcinoma by stimulating cell migration and EphB4 might be a potential therapeutic target in papillary thyroid carcinoma.
Assuntos
Carcinoma/genética , Movimento Celular/genética , Expressão Gênica , Receptor EphB4/genética , Neoplasias da Glândula Tireoide/genética , Animais , Carcinoma/metabolismo , Carcinoma/patologia , Carcinoma Papilar , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Camundongos , Metástase Neoplásica/genética , Fosfotransferases/metabolismo , Receptor EphB4/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Beta-catenin/TCF signaling has been reported to promote the growth and metastasis of pancreatic cancer cells. However, the regulation for the beta-catenin/TCF transcriptional complex remains largely unknown. Here, we have found that YEATS4 is a positive regulator for Beta-catenin/TCF signaling. The expression of YEATS4 was elevated in clinical pancreatic cancer samples and pancreatic cancer mouse model. Up-regulation of YEATS4 promoted the growth, migration and invasion of pancreatic cancer cells, while knocking down the expression of YEATS4 inhibited the growth, migration, invasion and metastasis of pancreatic cancer cells. Moreover, the mechanism study revealed that YEATS4 interacted with beta-catenin and activated beta-catenin/TCF signaling. Furthermore, knocking down the expression of YEATS4 impaired the malignant transformation of normal pancreatic cells (HPDE6C7) by the oncogenic Ras. Taken together, our study demonstrated the oncogenic roles of YEATS4 in the progression of pancreatic cancer by activating beta-catenin/TCF signaling and suggested that YEATS4 might be a promising therapeutic target for pancreatic cancer.