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

Molecular Cancer

Research

Cun-Cai Dai¹  Wen-Tao Gao¹  Zhu-Yin Qian¹  Jun-Li Wu¹  Kui-Rong Jiang¹  Qing Du²  Yi Zhu²  Ze-Kuan Xu²  Jing-Jing Zhang²  Yi Miao²  Jie Tang³  Zheng Li³  Kun-Ling Xie³  Yun-Peng Peng³  Jin-Qiu Tao³ 

[1] 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, 210029, Nanjing, People’s Republic of China;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, 210029, Nanjing, People’s Republic of China;Jiangsu Province Academy of Clinical Medicine, Institute of Tumor Biology, 300 Guangzhou Road, 210029, Nanjing, People’s Republic of China;The First School of Clinical Medicine, Nanjing Medical University, 140 Hanzhong Road, 210029, Nanjing, People’s Republic of China;

关键词: Yin Yang-1;    Pancreatic ductal adenocarcinoma;    Metastasis;    MMP10;    MUC4;    MEF2C;   

DOI  :  10.1186/1476-4598-13-130

 received in 2013-12-10, accepted in 2014-05-26,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundIncreasing 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.MethodsIn 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.ResultsWe 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Zhang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.