High levels of secreted frizzled-related protein 1 correlate with poor prognosis and promote tumourigenesis in gastric cancer |
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| Authors: | Ying Qu Partha S. Ray Jianfang Li Qu Cai Sanjay P. Bagaria Christopher Moran Myung-Shin Sim Jianian Zhang Roderick R. Turner Zhenggang Zhu Xiaojiang Cui Bingya Liu |
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| Affiliation: | 1. Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;2. Department of Surgery, University of Illinois College of Medicine at Urbana Champaign, Carle Cancer Center, Urbana, IL 61801, USA;3. Department of Surgery, Mayo Clinic Florida, Jacksonville, FL 32250, USA;4. Kaiser Permanente Northwest, Department of Surgery, Clackamas, OR 97015-9777, USA;5. Department of Biostatistics, John Wayne Cancer Institute, Santa Monica, CA 90404, USA;6. Department of Pathology, Saint John’s Health Center, Santa Monica, CA 90404, USA;7. Department of Surgery, Department of Obstetrics and Gynecology, Women’s Cancer Institute, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA |
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| Abstract: | ![]()
BackgroundSecreted 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.MethodsWe 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.ResultsWe 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 TGFβ (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.ConclusionOur 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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| Keywords: | sFRP1 Epithelial–mesenchymal transition Gastric cancer Metastasis TGFβ |
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