Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism

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• 作者：Jing-Jing Zhang (5) (6)
  Yi Zhu (5) (6)
  Kun-Ling Xie (7)
  Yun-Peng Peng (7)
  Jin-Qiu Tao (7)
  Jie Tang (7)
  Zheng Li (7)
  Ze-Kuan Xu (5) (6)
  Cun-Cai Dai (5)
  Zhu-Yin Qian (5)
  Kui-Rong Jiang (5)
  Jun-Li Wu (5)
  Wen-Tao Gao (5)
  Qing Du (5) (6)
  Yi Miao (5) (6)
  
  5. Department of General Surgery ; The first Affiliated Hospital of Nanjing Medical University ; Jiangsu Province Academy of Clinical Medicine ; Institute of Tumor Biology ; 300 Guangzhou Road ; Nanjing ; 210029 ; People鈥檚 Republic of China
  6. Jiangsu Province Academy of Clinical Medicine ; Institute of Tumor Biology ; 300 Guangzhou Road ; Nanjing ; 210029 ; People鈥檚 Republic of China
  7. The First School of Clinical Medicine ; Nanjing Medical University ; 140 Hanzhong Road ; Nanjing ; 210029 ; People鈥檚 Republic of China
  
• 关键词：Yin Yang ; 1 ; Pancreatic ductal adenocarcinoma ; Metastasis ; MMP10 ; MUC4 ; MEF2C
• 刊名：Molecular Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：1
• 全文大小：1,489 KB
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• 刊物主题：Cancer Research; Oncology;
• 出版者：BioMed Central
• ISSN：1476-4598

文摘

Background Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified. Methods In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software. Results We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. Conclusions The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.