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转胶蛋白促进癌症干细胞的迁移和侵袭。

Transgelin promotes migration and invasion of cancer stem cells.

机构信息

School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

出版信息

J Proteome Res. 2010 Oct 1;9(10):5108-17. doi: 10.1021/pr100378z.

DOI:10.1021/pr100378z
PMID:20707403
Abstract

Recent studies have suggested the existence of a small subset of cancer cells called cancer stem cells (CSCs), which possess the ability to initiate malignancies, promote tumor formation, drive metastasis, and evade conventional chemotherapies. Elucidation of the specific signaling pathway and mechanism underlying the action of CSCs might improve the efficacy of cancer treatments. In this study, we analyzed differentially expressed proteins between tumerigenic and nontumorigenic cells isolated from the human hepatocellular carcinoma (HCC) cell line, Huh7, via proteomic analysis to identify proteins correlated with specific features of CSCs. The expression level of Transgelin was 25-fold higher in tumorigenic cells than nontumorigenic cells. Similar results were also observed in tumorigenic cells derived from colorectal adenocarcinoma and prostate carcinoma. More importantly, the elevated levels of Transgelin significantly increased the invasiveness of tumorigenic cells, whereas reduced levels decreased the invasive potential. Moreover, in tumors derived from Huh7-induced xenografts, Transgelin was also co-expressed with CXCR4, which is responsible for tumor invasion. Taken together, these results indicate that the metastatic potential of CSCs arises from highly expressed Transgelin.

摘要

最近的研究表明,癌症细胞中存在一小部分被称为癌症干细胞(CSCs)的细胞,它们具有引发恶性肿瘤、促进肿瘤形成、驱动转移以及逃避常规化疗的能力。阐明 CSCs 作用的特定信号通路和机制可能会提高癌症治疗的效果。在这项研究中,我们通过蛋白质组学分析分析了从人肝癌(HCC)细胞系 Huh7 中分离的致瘤细胞和非致瘤细胞之间差异表达的蛋白质,以鉴定与 CSCs 特定特征相关的蛋白质。Transgelin 在致瘤细胞中的表达水平比非致瘤细胞高 25 倍。在源自结直肠腺癌和前列腺癌的致瘤细胞中也观察到了类似的结果。更重要的是,Transgelin 水平的升高显著增加了致瘤细胞的侵袭性,而降低水平则降低了侵袭潜能。此外,在源自 Huh7 诱导的异种移植的肿瘤中,Transgelin 也与负责肿瘤侵袭的 CXCR4 共表达。综上所述,这些结果表明 CSCs 的转移潜力源于高度表达的 Transgelin。

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