title: DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.
abstract: Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ding-Li
authors.initials: DL
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Hu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Kan
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Zu-Guo
authors.initials: ZG
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D011379:Prognosis; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D053323:Receptors, Tumor Necrosis Factor, Member 6b; D051785:Smad Proteins; C509044:TGFB3 protein, human; C505911:TNFRSF6B protein, human; D053782:Transforming Growth Factor beta3
keywords: TGF-β3/SMAD signaling; colorectal cancer; decoy receptor 3; epithelial-mesenchymal transition; metastasis