Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways.
Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways.
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Trop2通过ERK和JNK途径诱导MMP2增强甲状腺癌的侵袭
DOI：
10.1186/s12885-017-3475-2
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发表时间：
2017-07-14
期刊：
影响因子：
3.8
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Guan H;Guo Z;Liang W;Li H;Wei G;Xu L;Xiao H;Li Y
背景越来越多的证据表明，肿瘤相关钙信号转导器2（Trop2）在各种人类癌症中表达上调，并在肿瘤发生中发挥重要作用。然而，Trop2在甲状腺癌中的表达状态和功能意义尚不清楚。方法我们首先利用癌症基因组图谱(TCGA)网站上存放的甲状腺癌RNAseqV2数据集确定Trop2的表达。然后通过实时逆转录聚合酶链反应（RT-PCR）和免疫组织化学检测证实了 Trop2 的表达。通过进行 Transwell 和伤口愈合测定来评估细胞侵袭和迁移。此外，我们通过使用实时RT-PCR、Western blot、酶谱法和荧光素酶报告基因检测来探索其潜在机制。结果在本研究中，我们证明Trop2的表达在甲状腺癌中显着升高，并且其表达水平与肿瘤淋巴结转移（TNM）分期和N分类相关。 Trop2 的失调改变了甲状腺癌细胞的侵袭能力。进一步的机制研究表明，Trop2 上调了 MMP2 的表达。此外，我们发现 Trop2 的作用依赖于 ERK 和 JNK 通路。临床标本结果表明，原发性甲状腺癌中Trop2表达与MMP2表达相关。结论当前研究表明，Trop2表达升高可能是与甲状腺癌进展具有生物学和临床相关性的重要分子标志。
BackgroundMounting evidence has showed that Tumor-associated calcium signal transducer 2 (Trop2) is upregulated in various kinds of human cancers and plays important roles in tumorigenesis. However, the expression status and functional significance of Trop2 in thyroid cancer are largely unknown.MethodsWe first determined the expression of Trop2 by using RNAseqV2 data sets for thyroid cancer deposited on The Cancer Genome Atlas (TCGA) website. The expression of Trop2 was then confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. Cell invasion and migration were assessed by conducting Transwell and wound healing assays. Furthermore, we explored the underlying mechanisms by using real-time RT-PCR, Western blot, zymography, and luciferase reporter assays.ResultsIn this study, we demonstrated that the expression of Trop2 was significantly elevated in thyroid cancer and that its expression level was correlated with the tumor-node-metastasis (TNM) staging and N classification. Dysregulation of Trop2 altered the invasive capability of thyroid cancer cells. Further mechanistic study revealed that MMP2 expression was upregulated by Trop2. Moreover, we found that the effects of Trop2 were dependent on ERK and JNK pathways. The results from clinical specimens showed that Trop2 expression correlated with MMP2 expression in primary thyroid cancer.ConclusionThe current study suggests that elevated expression of Trop2 may represent an important molecular hallmark that is biologically and clinically relevant to the progression of thyroid cancer.
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影响因子：
--
作者：
Liang W;Guan H;He X;Ke W;Xu L;Liu L;Xiao H;Li Y
通讯作者：
Li Y
影响因子：
5.8
作者：
KARGA, H;LEE, JK;JAMESON, JL
通讯作者：
JAMESON, JL
影响因子：
8
作者：
Trerotola, M.;Cantanelli, P.;Alberti, S.
通讯作者：
Alberti, S.
影响因子：
3.3
作者：
Ning, Shanglei;Liang, Nan;Xin, Tao
通讯作者：
Xin, Tao
影响因子：
1.3
作者：
Addati, T.;Achille, G.;Simone, G.
通讯作者：
Simone, G.