Oncotarget

Research Papers:

FOXD3 regulates anaplastic thyroid cancer progression

Huabin Yin, Tong Meng, Lei Zhou, Feixing Zhao, Xiufang Li, Yundong Li, Mengjun Hu, Haiyan Chen and Dianwen Song _

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Oncotarget. 2017; 8:33644-33651. https://doi.org/10.18632/oncotarget.16853

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Abstract

Huabin Yin1,*, Tong Meng1,*, Lei Zhou2,*, Feixing Zhao3, Xiufang Li3, Yundong Li4, Mengjun Hu3, Haiyan Chen5, Dianwen Song1

1Department of Orthopedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China

2Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China

3Zhuji People’s Hospital of Zhejiang Province, Zhuji, Zhejiang, PR China

4Department of General Surgery, Haiyang People’s Hospital, Haiyang, Shangdong, PR China

5Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, PR China

*The authors contributed equally to this work

Correspondence to:

Yundong Li, email: yundong_li6228@163.com

Mengjun Hu, email: mengjun_hu@163.com

Haiyan Chen, email: haiyan_chen7678@163.com

Dianwen Song, email: Dianwen_Song@163.com

Keywords: FOXD3, human anaplastic thyroid cancer, metastasis, MAPK/ERK signal pathway

Received: February 09, 2017     Accepted: March 27, 2017     Published: April 05, 2017

ABSTRACT

Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis. It was reported that Forkhead box D3 (FOXD3) transcription factor is associated with several cancers. We investigated its antitumorigenic role of ATC in this study. The ATC cell lines SW1736 and K18 exhibited lower FOXD3 expression than the Nthy-ori-3-1 normal thyroid cell line. FOXD3 downregulation in ATC cell lines promoted invasiveness and epithelial-to-mesenchymal transition (EMT) and decreased cellular apoptosis. FOXD3 silencing also enhanced p-ERK levels in the ATC cell lines, suggesting it negatively regulated MAPK/ERK signaling. Silencing FOXD3 in SW1736 cells also led to generation of larger xenograft tumors with high p-ERK and low E-cadherin levels. Moreover, human ATC samples showed lower FOXD3 and higher p-ERK levels than samples of normal thyroid tissue. These findings demonstrate that FOXD3 acts as a tumor suppressor during anaplastic thyroid carcinogenesis and highlight its potential for clinical application.


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