Twist1 regulates the epithelial-mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma.
Expression of the oncogene Twist1 is correlated with tumor development and metastasis. Recent studies have suggested that the epithelial-to-mesenchymal transition (EMT) is necessary for tumor progression and metastases. Little is known concerning the role of Twist1 and EMT in thyroid cancer. In the present work, the expression levels of Twist1 and one marker of EMT, vimentin, were measured in papillary thyroid carcinoma (PTC). The results showed Twist1 expression to be correlated only with cancer lymph node metastases (P = 0.004) and not with other clinicopathological indicators. Moreover, Twist1 expression was positively correlated with the expression of vimentin (r = 0.408, P = 0.003). In vitro studies further indicated that reducing Twist1 expression using short hairpin RNA against Twist1 can decrease the invasive and metastatic properties of PTC cells and that the down-regulation of Twist1 can reverse EMT by increasing the expression of E-cadherin and down-regulating the expression of vimentin in the PTC cell line IHH-4. To investigate the effects on Twist1, the PTC cell lines TPC-1 and BCPAP were treated with TNF-α, resulting in Twist1 up-regulation that was dependent on NF-κB activation. After the inhibition of NF-κB activity with Bay11-7082, the Twist1 mRNA and protein levels could not be increased. The decline in the Twist1 mRNA and protein levels rendered the cancer cells less invasive. Thus, we conclude that Twist1 plays an important role in the EMT of PTC via the NF-κB pathway.
Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, 110001, China.
Nannan
N
Lv
Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, 110001, China. shanzhongyan@medmail.com.cn.
Zhongyan
Z
Shan
Research Center of Stem Cell, He Eye Hospitals, He University, Shenyang, 110163, China. yungao2000@hotmail.com.
Yun
Y
Gao
Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, 110001, China.
Haixia
H
Guan
Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, 110001, China.
Chenling
C
Fan
Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, 110001, China.
Hong
H
Wang
Department of Endocrinology and Metabolism, The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, 110001, China.
Weiping
W
Teng
D000293:Adolescent; D000328:Adult; D000368:Aged; D015820:Cadherins / Q000096:biosynthesis; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009570:Nitriles / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D013450:Sulfones / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics; D055815:Young Adult
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D015820:Cadherins; D016328:NF-kappa B; D009570:Nitriles; D009687:Nuclear Proteins; D013450:Sulfones; C103173:TWIST1 protein, human; D014409:Tumor Necrosis Factor-alpha; D051879:Twist-Related Protein 1; D014746:Vimentin
EMT; NF-κB; PTC; Twist1