Thioredoxin 1 mediates TGF-β-induced epithelial-mesenchymal transition in salivary adenoid cystic carcinoma
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Yang Jiang1, Xin Feng2, Lei Zheng1, Sheng-Lin Li3, Xi-Yuan Ge3, Jian-Guo Zhang1
1Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, PR China
2Department of Otolaryngology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
3Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, PR China
Jian-Guo Zhang, e-mail: [email protected]
Xi-Yuan Ge, e-mail: [email protected]
Keywords: thioredoxin 1, epithelial-mesenchymal transition, metastasis, TGF-β, salivary adenoid cystic carcinoma
Received: March 02, 2015 Accepted: August 07, 2015 Published: August 17, 2015
Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC) which is characterized by wide local infiltration, perineural spread, a propensity to local recurrence and late distant metastasis. Our recent studies have disclosed that TGF-β is a crucial factor for EMT in metastatic SACC. In this study, we further uncovered small redox protein thioredoxin 1 (TXN) as a critical mediator of TGF-β induced EMT. Immunohistochemistry analysis revealed significantly higher expressions of TXN, thioredoxin reductase 1 (TXNRD1) and N-cadherin, and lower expression of E-cadherin in human metastatic SACC compared to non-metastatic SACC tissues. Consistently, cultured SACC cells with stable TXN overexpression had decreased E-cadherin and increased N-cadherin as well as Snail and Slug expressions. The enhanced migration and invasion potential of these cells was abrogated by Akt or TXNRD1 inhibitors. Expression of N-cadherin and Akt p-Akt decreased, whereas E-cadherin expression increased in a BBSKE (TXNRD1 inhibitor)-dose-dependent manner. In a xenograft mouse model, TXN overexpression facilitated the metastatic potential of SACC-83 cells to the lung. Our results indicate that TXN plays a key role in SACC invasion and metastasis through the modulation of TGF-β-Akt/GSK-3β on EMT. TXN could be a potential therapeutic target for SACC.
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