【摘 要】
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Background Secreted frizzled-related protein 1 (sFRP1), Wnt signaling regulator, can positively or negatively regulate tumorigenesis and progression.We sought to determine the clinical relevance and t
【机 构】
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上海交通大学医学院附属瑞金医院,上海消化外科研究所,上海市胃肿瘤重点实验室,上海200025
【出 处】
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第9届全国胃癌学术会议暨第二届阳光长城肿瘤学术会议
论文部分内容阅读
Background Secreted frizzled-related protein 1 (sFRP1), Wnt signaling regulator, can positively or negatively regulate tumorigenesis and progression.We sought to determine the clinical relevance and the role of sFRP 1 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 sFRP 1 and coexpressed genes were analyzed 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.Immunofluorescence staining, qRT-PCR, immunoblotting and RhoGTPase activity assays were used to investigate the mechanisms of sFRP 1 overexpression.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 activates the TGFβ signaling pathway and thereby induces cell proliferation, epithelial-mesenchymal transition (EMT), and invasion.Conversely, sFRP1 knockdown shows the opposite effects.Furthermore, sFRP1 overexpression promotes tumorigenesis and metastasis in a xenograft model.We also show that Racl/GSK3β mediates the activation of TGFβ signaling by sFRP1 and suppresses the anti-tumor effect of TGFβ signaling while potentiating its pro-tumor function.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 TGFβ pathways which underlies gastric cancer development and progression.
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