LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression.
LYAR promotes colorectal cancer cell mobility by activating galectin-1 expression.
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LYAR 通过激活 galectin-1 表达来促进结直肠癌细胞迁移。
DOI：
10.18632/oncotarget.5335
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
Zhao Q
中科院分区：
文献类型：
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作者：
Wu Y;Liu M;Li Z;Wu XB;Wang Y;Wang Y;Nie M;Huang F;Ju J;Ma C;Tan R;Zen K;Zhang CY;Fu K;Chen YG;Wang MR;Zhao Q
结直肠癌（CRC）是全球癌症相关死亡的主要原因之一。然而，CRC发病机制的分子机制尚未完全了解。在这项研究中，我们报告了LYAR（Ly-1抗体反应性克隆）作为人CRC细胞迁移和侵袭的关键调节因子的特征。免疫组化结果显示，LYAR在转移性结直肠癌组织中的表达水平较高。我们发现LYAR促进了CRC细胞的迁移和侵袭能力。CRC细胞的基因表达谱分析表明，编码半乳糖凝集素-1蛋白的LGALS 1是LYAR的潜在靶点。ChIP分析和基因报告基因分析表明，LYAR直接结合LGALS 1启动子。galectin-1的异位表达部分恢复了LYAR敲低细胞的移动的潜能，这表明galectin-1有助于LYAR促进的CRC细胞的细胞迁移和侵袭。因此，这项研究揭示了一种新的机制，通过这种机制，转录因子LYAR可以通过上调CRC中半乳糖凝集素-1基因的表达来促进肿瘤细胞的迁移和侵袭。
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms of CRC pathogenesis are not fully understood. In this study, we report the characterization of LYAR (Ly-1 antibody reactive clone) as a key regulator of the migration and invasion of human CRC cells. Immunohistochemistry analysis demonstrated that LYAR is expressed at a higher level in metastatic CRC tissues. We found that LYAR promoted the migratory and invasive capabilities of CRC cells. Gene expression profile analysis of CRC cells showed that LGALS1, which encodes the galectin-1 protein, was a potential target of LYAR. The ChIP assay and gene reporter assays indicated that LYAR directly bound to the LGALS1 promoter. The ectopic expression of galectin-1 partially restored the mobile potential of LYAR knocked-down cells, which suggests that galectin-1 contributed to the LYAR-promoted cell migration and invasion of CRC cells. Thus, this study revealed a novel mechanism by which the transcription factor LYAR may promote tumor cell migration and invasion by upregulating galectin-1 gene expression in CRC.