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Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma

Endocrine volume 51, pages 469–477 (2016)Cite this article

Abstract

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.

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Acknowledgments

The authors would like to thank Dr. Bryan R. Haugen (Division of Endocrinology, Diabetes and Metabolism, University of Colorado, Denver, CO, USA) for TPC-1 support. This work was supported by grants from the National Science Foundation of China (No. 81102471).

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    Affiliations

    1. 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 Lv, Zhongyan Shan, Haixia Guan, Chenling Fan, Hong Wang & Weiping Teng

    2. Research Center of Stem Cell, He Eye Hospitals, He University, Shenyang, 110163, China

      Yun Gao

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    1. Nannan Lv
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    Correspondence to Zhongyan Shan or Yun Gao.

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    The authors have no conflicts of interest to report.

    Ethical approval

    The human thyroid tissue samples used in this study were initially retrieved from the Department of Pathology, Shenyang Feng Tian Hospital (Shenyang, Liaoning, People’s Republic of China), and the protocol was approved by the Ethics Committee of Feng Tian Hospital.

    Exclusivity Statement

    This work has not been published before and is not being submitted to any other journal. All of the authors have read the manuscript and have approved it for publication.

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    Zhongyan Shan and Yun Gao contributed equally to this work as co-corresponding authors.

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    Lv, N., Shan, Z., Gao, Y. et al. Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma. Endocrine 51, 469–477 (2016). https://doi.org/10.1007/s12020-015-0714-7

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    • DOI: https://doi.org/10.1007/s12020-015-0714-7

    Keywords

    • Twist1
    • PTC
    • EMT
    • NF-κB