S100A6 Protein Negatively Regulates CacyBPSIP-Mediated Inhibition of Gastric Cancer Cell Proliferation and Tumorigenesis 英文参考文献.docVIP

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S100A6 Protein Negatively Regulates CacyBPSIP-Mediated Inhibition of Gastric Cancer Cell Proliferation and Tumorigenesis 英文参考文献.doc

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S100A6 Protein Negatively Regulates CacyBPSIP-Mediated Inhibition of Gastric Cancer Cell Proliferation and Tumorigenesis 英文参考文献

S100A6ProteinNegativelyRegulatesCacyBP/SIP- MediatedInhibitionofGastricCancerCellProliferation andTumorigenesis XiaoxuanNing1*.,ShirenSun2.,KunZhang4,JieLiang3,YucaiChuai1,YuanLi1*,XiaomingWang1* 1DepartmentofGeriatrics,XijingHospital,FourthMilitaryMedicalUniversity,Xi’an,Shaanxi,China,2DepartmentofNephrology,XijingHospital,FourthMilitaryMedical University,Xi’an,Shaanxi,China,3StateKeyLaboratoryofCancerBiologyandInstituteofDigestiveDiseases,XijingHospital,FourthMilitaryMedicalUniversity,Xi’an, Shaanxi,China,4CollegeofLifeScience,ShaanxiNormalUniversity,Xi’an,Shaanxi,China Abstract Calcyclin-binding protein (CacyBP/SIP), identified on the basis of its ability to interact with S100 proteins in a calcium- dependent manner, was previously found to inhibit the proliferation and tumorigenesis of gastric cancer cells in our laboratory. Importantly, the effects of S100 proteins on the biological behavior of CacyBP/SIP in gastric cancer remain unclear. Herein, we report the construction of eukaryotic expression vectors for wild-type CacyBP/SIP and a truncated mutant lacking the S100 protein binding domain (CacyBP/SIPDS100). The expressions of the wild-type and truncated recombinant proteins were demonstrated by transfection of MKN45 gastric cancer cells. Co-immunoprecipitation assays demonstratedinteractionbetweenS100A6andwild-typeCacyBP/SIPinMKN45cells.RemovaloftheS100proteinbinding domaindramaticallyreducedtheaffinityofCacyBP/SIPforS100proteinsasindicatedbyreducedco-immunoprecipitation of S100A6 by CacyBP/SIPDS100. The MTT assay, FACS assay, clonogenic assay and tumor xenograft experiment were performed to assess the effect of CacyBP/SIP on cell growth and tumorigenesis in vitro and in vivo. Overexpression of CacyBP/SIPinhibitedtheproliferationandtumorigenesisofMKN45gastriccancercells;theproliferationandtumorigenesis rates were even further reduced by the expression of CacyBP/SIPDS100. We also showed that S100 proteins negatively regulate CacyBP/SIP-mediated inhibition o