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http://purl.uniprot.org/citations/28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28534984http://www.w3.org/2000/01/rdf-schema#comment"Lymph node metastasis in patients with urinary bladder cancer (UBC) is always associated with poor prognosis and is the determinant for tumor staging and the development of treatment regimens; however, its underlying mechanisms remain to be studied. Immunohistochemical staining of tumor sections from 62 UBC patients was performed using CCR7, D2-40 and CD34 antibodies. We showed that increased CCR7 expression was significantly associated with positive lymph node status (P=0.008), pT3-T4 tumor stage (P=0.015), tumor grade (P=0.010) and worse overall survival (OS, P<0.001) and that both CCR7 expression and lymph node metastasis were independent prognostic factors for OS (P=0.031 and P=0.001, respectively) based on multivariate analysis. We found that there was a significant association between MLVD and lymph node status (P=0.006), but this relation was not observed for MVD. Furthermore, we showed that increased CCR7 expression correlated significantly with higher MLVD (P=0.014) and MVD (P=0.002). Wound-healing and matrigel transwell assays indicated that activation of CCR7 with CCL21 significantly enhanced the invasion and migration abilities of UM-UC-3 cells, and this enhanced effect was significantly abrogated by CCR7 knockdown using siRNA. Western blot analysis revealed that the phospho-ERK1/2 level was markedly increased when UM-UC-3 cells were treated with CCL21 and significantly decreased when the CCR7 gene was silenced. MEK/ERK1/2 inhibition with PD98059 significantly suppressed the migration and invasion abilities of UM-UC-3 cells and also significantly abrogated the effects of CCL21/CCR7 on cell migration and invasion. Based on these results, we conclude that activation of the CCL21/CCR7 chemoaxis promotes lymph node metastasis of UBC in at least two ways. Firstly, although CCR7 is a promoting factor that induces both lymphangiogenesis and angiogenesis, it may promote lymph node metastasis through its lymphangiogenic effect rather than through its angiogenic effect. Secondly, the CCL21/CCR7 chemoaxis promotes the migration and invasion of UBC cells via the MEK/ERK1/2 signaling pathway rather than the PI3K/AKT pathway."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.org/dc/terms/identifier"doi:10.3892/ijo.2017.4003"xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Chen Z."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Chen W."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Feng D."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Jiang H."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Li X."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Zhang X."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Xiong Y."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/author"Huang F."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/name"Int J Oncol"xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/pages"75-90"xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/title"CCL21/CCR7 interaction promotes cellular migration and invasion via modulation of the MEK/ERK1/2 signaling pathway and correlates with lymphatic metastatic spread and poor prognosis in urinary bladder cancer."xsd:string
http://purl.uniprot.org/citations/28534984http://purl.uniprot.org/core/volume"51"xsd:string
http://purl.uniprot.org/citations/28534984http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28534984
http://purl.uniprot.org/citations/28534984http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/28534984
http://purl.uniprot.org/uniprot/#_B4DFY5-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984
http://purl.uniprot.org/uniprot/#_A0N0Q0-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984
http://purl.uniprot.org/uniprot/#_A4QPA9-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984
http://purl.uniprot.org/uniprot/#_B2R6V6-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984
http://purl.uniprot.org/uniprot/#_J3KSS9-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984
http://purl.uniprot.org/uniprot/#_P32248-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984
http://purl.uniprot.org/uniprot/#_O00585-mappedCitation-28534984http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28534984