Thioredoxin 1 mediates TGF-β-induced epithelial-mesenchymal transition in salivary adenoid cystic carcinoma

Oncotarget
Yang JiangJian-Guo Zhang

Abstract

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 indic...Continue Reading

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Citations

Jul 2, 2016·Journal of Clinical Medicine·Aristidis Moustakas, Carl-Henrik Heldin
Feb 24, 2017·Frontiers in Physiology·Madeline MidgettSandra Rugonyi
Sep 13, 2019·Journal of Cellular and Molecular Medicine·Laura TomaselloCarla Giordano
Sep 10, 2021·Genetics, Selection, Evolution : GSE·Christos DadousisJohn M Hickey
Sep 21, 2021·Antioxidants & Redox Signaling·Fernando T OgataHugo P Monteiro

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Methods Mentioned

BETA
dissection
transfection
xenograft
light microscopy

Software Mentioned

Quantity One
SPSS

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