Tropomyosin3 overexpression and a potential link to epithelial-mesenchymal transition in human hepatocellular carcinoma.
Tropomyosin3 overexpression and a potential link to epithelial-mesenchymal transition in human hepatocellular carcinoma.
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DOI：
10.1186/1471-2407-10-122
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发表时间：
2010-04-01
期刊：
影响因子：
3.8
通讯作者：
Chung YJ
中科院分区：
文献类型：
--
作者：
Choi HS;Yim SH;Xu HD;Jung SH;Shin SH;Hu HJ;Jung CK;Choi JY;Chung YJ
由于肝细胞癌是世界范围内癌症死亡的主要原因之一，了解肝癌的发生机制和寻找有效的肿瘤进展标志物对改善预后仍具有重要意义。Tropmyosin3(TPM3)在肝细胞癌中的扩增和过度表达是常见的现象，但其生物学意义尚未明确。在本研究中，我们旨在阐明TPM3的作用及其相关分子机制。将TPM3-siRNA导入过表达TPM3的肝癌细胞株HepG2和SNU-475中。实时荧光定量聚合酶链式反应和针对TPM3的Western blotting验证了TPM3基因的敲除。用跨膜法检测细胞的迁移和侵袭能力。通过集落形成和软琼脂实验检测细胞生长能力。沉默TPM3可显著抑制两种肝癌细胞系的迁移和侵袭能力。为了阐明抑制迁移和侵袭的机制，我们检测了TPM3基因敲除后与上皮-间充质转化(EMT)相关的Snail和E-cadherin的表达水平。在TPM3基因敲除细胞中，与阴性对照相比，E-钙粘蛋白表达显著上调，Snail表达显著下调。TPM3基因敲除也抑制了肝癌细胞的集落形成和贴壁非依赖性生长。基于我们的发现，我们提出了一个假设，即TPM3的过表达激活了Snail介导的EMT，这将抑制E-钙粘蛋白的表达，并在肝癌发生过程中赋予肝癌细胞迁移或侵袭的潜力。据我们所知，这是TPM3通过改变EMT途径参与肝癌细胞迁移和侵袭的第一个证据。
Since hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, it is still important to understand hepatocarcinogenesis mechanisms and identify effective markers for tumor progression to improve prognosis. Amplification and overexpression of Tropomyosin3 (TPM3) are frequently observed in HCC, but its biological meanings have not been properly defined. In this study, we aimed to elucidate the roles of TPM3 and related molecular mechanisms. TPM3-siRNA was transfected into 2 HCC cell lines, HepG2 and SNU-475, which had shown overexpression of TPM3. Knockdown of TPM3 was verified by real-time qRT-PCR and western blotting targeting TPM3. Migration and invasion potentials were examined using transwell membrane assays. Cell growth capacity was examined by colony formation and soft agar assays. Silencing TPM3 resulted in significant suppression of migration and invasion capacities in both HCC cell lines. To elucidate the mechanisms behind suppressed migration and invasiveness, we examined expression levels of Snail and E-cadherin known to be related to epithelial-mesenchymal transition (EMT) after TPM3 knockdown. In the TPM3 knockdown cells, E-cadherin expression was significantly upregulated and Snail downregulated compared with negative control. TPM3 knockdown also inhibited colony formation and anchorage independent growth of HCC cells. Based on our findings, we formulate a hypothesis that overexpression of TPM3 activates Snail mediated EMT, which will repress E-cadherin expression and that it confers migration or invasion potentials to HCC cells during hepatocarcinogenesis. To our knowledge, this is the first evidence that TPM3 gets involved in migration and invasion of HCCs by modifying EMT pathway.
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影响因子：
13.5
作者：
Llovet, Josep M.;Bruix, Jordi
通讯作者：
Bruix, Jordi
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8.8
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作者：
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Fletcher, JA
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