S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition.
S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition.
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S100A4-MYH9轴通过诱导TGF-β介导的上皮-间质转化促进胃癌细胞的迁移和侵袭
DOI：
10.7150/jca.25469
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发表时间：
2018
影响因子：
3.9
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Li F;Shi J;Xu Z;Yao X;Mou T;Yu J;Liu H;Li G
导致进展期胃癌腹膜转移的驱动基因尚不清楚。提示S100 A4在胃肠道肿瘤转移过程中起重要作用，本研究旨在探讨S100 A4在进展期胃癌转移中的作用及其可能机制。应用siRNA或cDNA转染来改变蛋白S100 A4和MYH 9的表达，随后研究上皮和间质转化（EMT）相关标志物的表达。细胞迁移实验检测S100 A4和MYH 9对细胞迁移能力的影响。对组织样本芯片进行免疫组化分析，以揭示其与临床病理参数的关系和预测生存的潜在能力。S100 A4和MYH 9在腹膜转移灶和原发灶中的表达与癌旁正常组织相比具有一致性。S100 A4的低表达导致上皮标记物的增加，而间充质标记物的减少则是威尔斯的增加，而S100 A4的过表达则导致相反的影响。S100 A4表达与TGF-β刺激诱导的迁移能力增强和EMT过程密切相关。S100 A4的干扰可导致MYH 9表达下调，并通过参与EMT过程使Smad通路失活，而MYH 9的过表达可逆转这一过程。此外，S100 A4和MYH 9的共表达在组织芯片中被鉴定，并通过免疫荧光测定证实。结论：S100 A4及其下游分子MYH 9在进展期胃癌中的过表达预示着不良预后; S100 A4基因可促进TGF-β刺激诱导的EMT过程，提示其可能成为胃癌腹膜转移的治疗靶点。
Driver genes conducing to peritoneal metastasis in advanced gastric cancer remain to be clarified. S100A4 is suggested to evolve in metastasis of gastrointestinal cancer, we aim to explore the role of S100A4 plays in metastasis of advanced gastric cancer and the potential mechanism. Transfection of siRNA or cDNA was applied to alter the expression of protein S100A4 and MYH9, investigation of the expression of epithelial and mesenchymal transition (EMT) associated markers was followed. Cell migration assay was used to screen the alteration of migration ability regulated by S100A4 and MYH9. IHC analysis for tissue sample microarray was performed to reveal their relationship with clinical pathological parameters and potential capacity of predicting survival. Consistent overexpression of S100A4 and MYH9 were found in peritoneal metastasis and primary site compared with adjacent normal tissue. Low expression of S100A4 led to increased epithelial markers as wells as decline of mesenchymal makers, while overexpression of S100A4 led to inverse impact. S100A4 expression was closely correlated with increased migration ability and EMT process induced by TGF-β stimulation. Interference of S100A4 led to downregulation of MYH9 and inactivation of Smad pathway through participating in EMT process, which could be reversed by overexpression of MYH9. Moreover, co-expression of S100A4 and MYH9 was identified in tissue microarray and confirmed by immunofluorescence assay. In conclusion, overexpression of S100A4 and downstream molecular MYH9 in advanced gastric cancer predicted poor prognosis; oncogene S100A4 facilitate EMT process induced by TGF-β stimulation, suggesting a potential target in management of peritoneal metastasis of gastric cancer.
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乳腺癌活检中S100A4，E-钙粘蛋白，α-和β-catenin的表达。
影响因子：
8.8
作者：
Pedersen, KB;Nesland, JM;Fodstad, O;Mælandsmo, GM
通讯作者：
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影响因子：
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影响因子：
10.3
作者：
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通讯作者：
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