High levels of secreted frizzled-related protein 1 correlate with poor prognosis and promote tumourigenesis in gastric cancer
High levels of secreted frizzled-related protein 1 correlate with poor prognosis and promote tumourigenesis in gastric cancer
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高水平的分泌型卷曲相关蛋白 1 与不良预后相关并促进胃癌肿瘤发生
DOI：
10.1016/j.ejca.2013.07.011
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发表时间：
2013-11-01
影响因子：
8.4
通讯作者：
Liu, Bingya
中科院分区：
文献类型：
--
作者：
Qu, Ying;Ray, Partha S.;Liu, Bingya
背景资料：分泌型卷曲相关蛋白1（Secreted frizzled-related protein 1，sFRP 1）是Wnt信号转导的调节因子，对肿瘤的发生、发展具有积极或消极的调节作用。我们试图确定sFRP 1的临床相关性和在胃癌的发展和progress.Methods的作用：我们调查了sFRP 1蛋白的表达水平和其临床病理相关性使用85例人类胃标本的生存信息（JWCI队列）。使用131个样本的cDNA微阵列数据（瑞金队列）分析sFRP 1和共表达基因的mRNA水平。sFRP 1改变的影响进行了研究，使用细胞增殖，集落形成，迁移，侵袭和异种移植models.Results：我们发现，sFRP 1在一些人类癌症中过表达，并与淋巴结转移和胃癌患者的总生存率下降显着相关。使用胃癌细胞模型，我们证明sFRP 1过表达与TGF β（转化生长因子β）信号通路的激活相关，从而诱导细胞增殖，上皮-间质转化（EMT）和侵袭。相反，sFRP 1敲低显示出相反的效果。此外，sFRP 1过表达促进肿瘤的发生和转移在异种移植model.Conclusion：我们的研究表明，sFRP 1是一个生物标志物的侵袭性亚组的人胃癌和预后生物标志物与生存不良的患者。我们的数据提供了深入了解Wnt和TGF β通路之间的串扰，这是胃癌发生和发展的基础。(C)2013爱思唯尔有限公司保留所有权利。
Background: Secreted frizzled-related protein 1 (sFRP1), Wnt signalling regulator, can positively or negatively regulate tumourigenesis and progression. We sought to determine the clinical relevance and the role of sFRP1 in gastric cancer development and progression.Methods: We investigated the sFRP1 protein expression levels and its clinicopathological correlations using 85 cases of human gastric samples with survival information (JWCI cohort). mRNA levels of sFRP1 and coexpressed genes were analysed using 131-sample cDNA microarray data (Ruijin cohort). The effects of sFRP1 alteration were investigated using cell proliferation, colony formation, migration, and invasion and xenograft models.Results: We show that sFRP1 is overexpressed in some human cancers and is significantly associated with lymph node metastasis and decreased overall survival in gastric cancer patients. Using gastric cancer cell models, we demonstrate that sFRP1 overexpression is correlated with the activation of TGF beta (transforming growth factor-beta) signalling pathway and thereby induces cell proliferation, epithelial-mesenchymal transition (EMT), and invasion. Conversely, sFRP1 knockdown shows the opposite effects. Furthermore, sFRP1 overexpression promotes tumourigenesis and metastasis in a xenograft model.Conclusion: Our studies demonstrate that sFRP1 is a biomarker for aggressive subgroups of human gastric cancer and a prognostic biomarker for patients with poor survival. Our data provide insight into a crosstalk between Wnt and TGF beta pathways which underlies gastric cancer development and progression. (C) 2013 Elsevier Ltd. All rights reserved.