title: SDF-1/CXCR4 promotes epithelial-mesenchymal transition and progression of colorectal cancer by activation of the Wnt/β-catenin signaling pathway.
abstract: Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial-mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and β-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with β-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/β-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/β-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/β-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression.
authors.affiliation: Department of Respiration, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Hu
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Han
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zhi-Pin
authors.initials: ZP
authors.lastname: Ruan
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Kang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China. Electronic address: wsh2003@126.com.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China. Electronic address: nankj@163.com.
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Nan
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4; D051176:beta Catenin
keywords: CXCR4; Colorectal cancer; EMT; Invasion and metastasis; Wnt/β-catenin