Macrophage capping protein CapG is a putative oncogene involved in migration and invasiveness in ovarian carcinoma.

Macrophage capping protein CapG is a putative oncogene involved in migration and invasiveness in ovarian carcinoma.
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DOI:
10.1155/2014/379847
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发表时间:
2014
影响因子:
--
通讯作者:
Fleisch MC
Fleisch MC
中科院分区:
生物学3区
文献类型:
--
作者:
Glaser J;Neumann MH;Mei Q;Betz B;Seier N;Beyer I;Fehm T;Neubauer H;Niederacher D;Fleisch MC

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肌动蛋白结合蛋白CapG通过与细胞骨架相互作用调节细胞运动。CapG在不同的非肿瘤性肿瘤实体中与肿瘤进展有关,并且在乳腺癌细胞系中的过表达与体外更具侵袭性的表型相关。在这里,我们报告了qRealTime-PCR分析的18/47(38%)卵巢癌(OC)中显著的CapG过表达。通过siRNA介导的CapG敲低和CapG过表达对OC细胞系的功能分析显示,CapG依赖的细胞迁移和侵袭性。在CapG基因内发现了一个单核苷酸多态性rs6886,影响CapG磷酸化位点,从而可能改变CapG的功能。SNP rs6886 (c.1004A/G)的次要等位基因频率(MAF)较高,纯合子(A/A, His335)基因型在输卵管癌患者中的发生率(50%)明显高于对照组(10%)。由于卵巢癌是最致命的癌症疾病之一,检测诸如CapG等新的生物标志物可以揭示新的诊断和治疗靶点。此外,深入分析与FTC和OC相关的SNP rs6886将有助于更好地了解OC的癌变和进展。
The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.
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