title: PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF-κB/MMP-9 signaling pathway.
abstract: BACKGROUND
  PinX1 (PIN2/TRF1-interacting telomerase inhibitor 1) was suggested to be correlated with tumor progression. This study was designed to evaluate the role of PinX1 in human breast cancer.
  
  
  METHODS
  To evaluate the function of PinX1 in breast cancer, we used a tissue microarray (TMA) of 405 human breast cancer patients and immunohistochemistry to analyze the correlation between PinX1 expression and clinicopathologic variables and patient survival. We also detected the abilities of cell migration and invasion in breast cancer by performing cell migration and invasion assay, gelatin zymography and western blot analysis. Lastly, we set up the nude mice model by Tail vein assay to exam the functional role of PinX1 in breast cancer metastasis.
  
  
  RESULTS
  We found that low PinX1 expression was associated with lymph node metastasis (P = 0.002) and histology grade (P = 0.001) in patients, as well as with poorer overall and disease-specific survival (P = 0.010 and P = 0.003, respectively). Moreover, we identified that PinX1 inhibited the migration and invasion of breast cancer by suppressing MMP-9 expression and activity via NF-κB-dependent transcription in vitro. Finally, our mice model confirmed that PinX1 suppressed breast cancer metastasis in vivo.
  
  
  CONCLUSIONS
  Our data revealed that low PinX1 expression was an independent negative prognostic factor for breast cancer patients. These findings suggested that PinX1 might be function as a tumor metastasis suppressor in the development and progression of breast cancer by regulating the NF-κB/MMP-9 signaling pathway, and might be a prognostic marker as well as a therapeutic target for breast cancer.
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. meilin-1018@163.com.|School of Medical Imaging, Xuzhou Medical College, Xuzhou, Jiangsu, China. meilin-1018@163.com.
authors.forename: Meilin
authors.initials: M
authors.lastname: Shi
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. cmh416@126.com.
authors.forename: Menghan
authors.initials: M
authors.lastname: Cao
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. piaoren7431@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Song
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. liuqinghua1@126.com.|Department of Pathology, Xuzhou Medical College, Xuzhou, Jiangsu, China. liuqinghua1@126.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. justinlee719@hotmail.com.|Department of Urology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. justinlee719@hotmail.com.
authors.forename: Hailong
authors.initials: H
authors.lastname: Li
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. mengfei870410@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Meng
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. zhen-qiang.pan@mssm.edu.|Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. zhen-qiang.pan@mssm.edu.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. bj@xzmc.edu.cn.|Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. bj@xzmc.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.affiliation: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. jnzheng@xzmc.edu.cn.|Department of Urology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China. jnzheng@xzmc.edu.cn.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D016328:NF-kappa B; C440808:PINX1 protein, human; D025521:Tumor Suppressor Proteins; D020780:Matrix Metalloproteinase 9