Transmembrane Protease Serine 4 Promotes Thyroid Cancer Proliferation via CREB Phosphorylation

Transmembrane Protease Serine 4 Promotes Thyroid Cancer Proliferation via CREB Phosphorylation
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跨膜蛋白酶丝氨酸 4 通过 CREB ​​磷酸化促进甲状腺癌增殖。

DOI：
10.1089/thy.2014.0155
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发表时间：
2015-01-01
期刊：
THYROID
影响因子：
6.6
通讯作者：
Li, Yanbing
Li, Yanbing
中科院分区：
医学1区
文献类型：
--
作者：
Guan, Hongyu;Liang, Weiwei;Li, Yanbing

文献摘要

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背景 跨膜丝氨酸蛋白酶4（TMPRSS 4）是II型跨膜丝氨酸蛋白酶（TTSP）之一，在各种癌症中升高，并且与多种恶性表型相关。然而，TMPRSS 4在甲状腺癌中的表达模式和生物学意义在很大程度上是未知的。在这项研究中，我们研究了TMPRSS 4在甲状腺癌中的表达，并评估了TMPRSS 4在甲状腺癌中的促增殖作用。 方法 采用免疫组化和实时荧光定量RT-PCR方法检测甲状腺癌组织中TMPRSS 4的表达。我们使用MTT、集落形成、锚定非依赖性生长、流式细胞术分析和5-乙炔基-2 '-脱氧尿苷（EdU）掺入测定来评估体外细胞增殖。通过Western blot、实时荧光定量RT-PCR和荧光素酶检测等方法研究其作用机制。 结果 TMPRSS 4在甲状腺癌中过表达，并与恶性程度相关。甲状腺癌细胞中TMPRSS 4的消耗显著抑制增殖。此外，TMPRSS 4过表达的甲状腺癌细胞的增殖显著增强。我们还表明，环磷酸腺苷反应元件结合蛋白（CREB）-细胞周期蛋白D1信号介导，至少部分，TMPRSS 4在甲状腺癌细胞增殖的作用。 结论 TMPRSS 4在甲状腺癌中过表达，TMPRSS 4-CREB信号传导是维持甲状腺癌细胞增殖所必需的。
BACKGROUND Transmembrane protease serine 4 (TMPRSS4), one of the type II transmembrane serine proteases (TTSPs), is elevated in various cancers and is associated with multiple malignant phenotypes. However, the expression pattern and biologic significance of TMPRSS4 in thyroid cancer are largely unknown. In this study, we investigated the expression of TMPRSS4 in thyroid cancer and assessed the pro-proliferative role of TMPRSS4 in thyroid cancer. METHODS Immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of TMPRSS4 in thyroid cancer. We evaluated in vitro cell proliferation using MTT, colony formation, anchorage-independent growth, flow cytometry analysis, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. Western blot, real-time RT-PCR, and luciferase assays were conducted to reveal the underlying mechanisms. RESULTS TMPRSS4 is overexpressed in thyroid cancer and is associated with the grade of malignancy. Depletion of TMPRSS4 in thyroid cancer cells significantly suppressed proliferation. Moreover, the proliferation of thyroid cancer cells with TMPRSS4 overexpression was significantly enhanced. We also show that cyclic adenosine monophosphate response element-binding protein (CREB)-cyclin D1 signaling mediates, at least partially, the role of TMPRSS4 in thyroid cancer cell proliferation. CONCLUSIONS TMPRSS4 is overexpressed in thyroid cancer and TMPRSS4-CREB signaling is needed to sustain thyroid cancer cell proliferation.