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Clinicopathologic significance of CXCR4 expressions in patients with esophageal squamous cell carcinoma
Institution:1. Department ofPathology, The First Hospital Affiliated with Shandong First Medical University, Jinan, China;2. Department of Pathology, LiaoCheng People’s Hospital, LiaoCheng, China;3. Department of General Surgery, Qilu Hospital of Shandong University, China;4. Shandong University Medical School, Jinan, Shandong, China;1. Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China;2. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China;1. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University Hospital, 3401 North Broad Street C-501, Philadelphia, PA 19140, USA;2. Department of Surgery, Temple University Hospital, 3401 North Broad Street C-501, Philadelphia, PA 19140, USA;3. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University Hospital, Temple University Health System, 3401 North Broad Street C-501, Philadelphia, PA 19140, USA;1. Department of Thoracic Surgery, The Second People’s Hospital of Nantong, Nantong, Jiangsu, China;2. Department of Radiation Oncology, Nantong Tumor Hospital, Nantong, Jiangsu, China
Abstract:AimsThis study was designed to investigate the biological function of CXCR4 in esophageal squamous cell carcinoma and to explore the underlying mechanism to provide potential targets for esophageal squamous cell carcinoma.MethodsA total of 101 patients with esophageal squamous cell carcinoma were included, and the relationship between CXCR4 and clinicopathological factors was analyzed. Laser scanning confocal microscopy was used to observe numbers of autophagosomes in TE-1 cell line and the ability of proliferation and invasion were evaluated meanwhile.ResultsCXCR4 is overexpressed in ESCC specimens and is associated with poor differentiation and lymphocyte metastasis. In the survival analysis, CXCR4 predicted a poor overall survival prognosis. The number of autophagosomes in the siR-CXCR4 group was decreased compared with negative group (P < 0.05), while was increased in the pcDNA3.1-CXCR4 group (P < 0.05).Western blot result show upregulation of LC3II, the ratio of LC3II/LC3I and Beclin1 in pcDNA3.1-CXCR4 group and decreased expression of LC3II, the ratio of LC3II/LC3I and Beclin1 in siR-CXCR4 group. Transwell assay show CXCR4 overexpression promote the invasion of TE-1 cells and was attenuated by autophagy inhibitor 3-Methyladenine.On the contrary, invasion cell numbers decreased in siR-CXCR4 group and was rescued by autophagy inducer Rapamycin.ConclusionCXCR4 is an indicator of poor prognosis for ESCC. CXCR4 promote autophagy and regulate cell invasion through autophagy in ESCC. Our study provides new insights for the treatment of esophageal squamous cell carcinoma and CXCR4 may serve as a therapeutic target for ESCC.
Keywords:Squamous cell carcinoma  CXCR4  Autophagy  Invasion
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