Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K.
Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K.
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Coronin 3通过上调MMP-9和组织蛋白酶K促进胃癌转移
DOI：
10.1186/1476-4598-11-67
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发表时间：
2012-09-14
期刊：
影响因子：
37.3
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Ren G;Tian Q;An Y;Feng B;Lu Y;Liang J;Li K;Shang Y;Nie Y;Wang X;Fan D
背景 Coronins 是一个高度进化保守的蛋白质家族，据报道参与肌动蛋白细胞骨架动力学的调节，尽管只有 Coronin 3 已被证明与癌细胞迁移相关。在胶质母细胞瘤细胞中，Coronin 3 的敲低会抑制细胞增殖和侵袭。 Coronin 3还与肝细胞癌的侵袭和转移有关。本文通过上调或下调Coronin 3表达后胃癌细胞的迁移、侵袭和转移能力进行分析，探讨Coronin 3在胃癌转移过程中的作用机制。结果本实验室建立的高转移亚细胞系MKN28-M中Coronin 3表达较高。我们还证明，Coronin 3 在淋巴结转移中的表达显着高于原发性胃癌组织，并且 Coronin 3 的过表达与临床分期的增加和淋巴结转移相关。编码 shRNA 的重组慢病毒载体旨在下调胃癌细胞系中的 Coronin 3 表达。该慢病毒载体稳定敲低coronin 3可有效抑制MKN45胃癌细胞的迁移和侵袭。相反，coronin 3 的上调显着增强 MKN28-NM 细胞的迁移和侵袭。此外，尾静脉注射胃癌细胞后，敲低Coronin 3可显着减少小鼠的肝转移。采用Human Tumor Metastasis PCR Array筛选下调Coronin 3鉴定的转移相关基因，结果提示，敲低Coronin 3后，MMP-9和组织蛋白酶K表达减少，抑制了肿瘤细胞的迁移和侵袭。结论Coronin 3在胃癌转移灶中高表达，并能促进转移。 胃癌细胞的行为，包括迁移和侵袭。
BackgroundCoronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics, although only coronin 3 has been shown to be related to cancer cell migration. In glioblastoma cells, the knockdown of coronin 3 inhibits cell proliferation and invasion. Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma. In this paper, we analyze the migration, invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3, and explore the mechanism of coronin 3 in the process of gastric cancer metastasis.ResultsThe expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M, which we established in our laboratory. We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues, and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis. Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines. Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells. In contrast, up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells. In addition, knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells. The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3, and the results suggested that, following the knockdown of coronin 3, the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K.ConclusionCoronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells, including their migration and invasion.
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