Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.
Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility.
复制标题
经凝蛋白在体内增加了结直肠癌细胞的转移潜力，并改变了与细胞运动的基因的表达。
DOI：
10.1186/s12885-016-2105-8
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发表时间：
2016-02-04
期刊：
影响因子：
3.8
通讯作者：
Lin Y
中科院分区：
文献类型：
--
作者：
Zhou HM;Fang YY;Weinberger PM;Ding LL;Cowell JK;Hudson FZ;Ren M;Lee JR;Chen QK;Su H;Dynan WS;Lin Y
Transgelin 是一种肌动蛋白结合蛋白，可促进正常细胞的运动。尽管转凝胶蛋白在癌症中的作用存在争议，但许多研究表明，其水平升高与侵袭性肿瘤行为、晚期和不良预后相关。在这里，我们试图通过确定结直肠癌（CRC）细胞中转凝胶蛋白水平的实验操作是否导致体内转移潜力的变化来更直接地确定转凝胶蛋白的作用。使用体外生长和侵袭性测定以及实验性转移的小鼠尾静脉测定来表征转凝胶蛋白表达不同的同基因CRC细胞系。通过基因表达谱和定量 PCR 研究转凝胶蛋白过表达的下游影响。内源水平较低的 RKO 细胞中转凝胶蛋白的稳定过表达导致侵袭性增加、低密度生长以及在软琼脂中生长。过度表达还导致小鼠尾静脉注射模型中肺转移的数量和大小增加。同样，在具有高内源水平的 HCT116 细胞中，转基因蛋白表达的减弱会减少同一模型中的转移。对 mRNA 表达模式的研究表明，转凝胶蛋白过度表达改变了大约 250 个其他转录物的水平，影响肌动蛋白或其他细胞骨架蛋白功能的基因过度表达。变化包括 HOOK1、SDCCAG8、ENAH/Mena 和 TNS1 的增加以及 EMB、BCL11B 和 PTPRD 的减少。转基因蛋白水平的增加或减少对肿瘤细胞行为具有相互影响，较高的表达促进转移。慢性过度表达会影响转移相关基因 mRNA 的稳态水平。本文的在线版本 (doi:10.1186/s12885-016-2105-8) 包含补充材料，可供授权用户使用。
Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo. Isogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR. Stable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over-representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD. Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes. The online version of this article (doi:10.1186/s12885-016-2105-8) contains supplementary material, which is available to authorized users.