FOXD3 regulates anaplastic thyroid cancer progression.
FOXD3 regulates anaplastic thyroid cancer progression.
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FOXD3 调节甲状腺未分化癌的进展。
DOI：
10.18632/oncotarget.16853
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发表时间：
2017-05-16
期刊：
影响因子：
--
通讯作者：
Song D
中科院分区：
文献类型：
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作者：
Yin H;Meng T;Zhou L;Zhao F;Li X;Li Y;Hu M;Chen H;Song D
甲状腺间变性癌(ATC)是一种侵袭性强、预后差的恶性肿瘤。据报道，Forkhead box D3(FOXD3)转录因子与多种癌症有关。在本研究中，我们研究了ATC的抗肿瘤作用。ATC细胞系SW1736和K18的FOXD3表达低于正常甲状腺细胞系Nthy-Ori-3-1。FOXD3下调促进ATC细胞的侵袭性和上皮向间充质转化(EMT)，减少细胞凋亡。FOXD3沉默也增加了ATC细胞中p-ERK的水平，表明它负调控MAPK/ERK信号转导。在SW1736细胞中沉默FOXD3也会导致较大的异种移植瘤的产生，这些肿瘤具有高p-ERK和低E-钙粘蛋白水平。此外，与正常甲状腺组织相比，人类ATC样本显示更低的FOXD3和更高的p-ERK水平。这些发现表明FOXD3在间变性甲状腺癌的发生过程中发挥了肿瘤抑制作用，并突出了其临床应用的潜力。
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.