Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism.
复制标题
Yin Yang-1通过MUC4/ErbB2/p38/MEF2C依赖性机制下调MMP10抑制胰腺导管腺癌的侵袭和转移
DOI：
10.1186/1476-4598-13-130
复制
发表时间：
2014-05-29
期刊：
影响因子：
37.3
通讯作者：
Miao Y
中科院分区：
文献类型：
--
作者：
Zhang JJ;Zhu Y;Xie KL;Peng YP;Tao JQ;Tang J;Li Z;Xu ZK;Dai CC;Qian ZY;Jiang KR;Wu JL;Gao WT;Du Q;Miao Y
越来越多的证据表明转录因子Yin Yang-1（YY 1）在人类肿瘤发生中起重要作用。然而，它在癌症中的功能仍然存在争议，YY 1与胰腺导管腺癌（PDAC）的相关性仍有待澄清。MethodsIn这项研究中，我们检测YY 1在临床PDAC组织样本和细胞系中的表达，采用定量RT-PCR，免疫组化和蛋白质印迹。我们还使用qRT-PCR检测了108份PDAC样本中MUC 4和MMP 10的mRNA水平，并分析了YY 1与MUC 4或MMP 10表达之间的相关性。采用CCK-8法、细胞迁移和侵袭实验研究YY 1对PDAC细胞增殖、侵袭和转移能力的影响。通过异种皮下移植模型和尾静脉转移模型研究胰腺肿瘤的体内生长和转移。通过数字基因表达（DGE）测序、信号转导通路阻断实验和荧光素酶检测，探讨了YY 1介导PDAC肿瘤进展的潜在机制。结果YY 1在PDACs中的表达明显高于癌旁组织和正常胰腺组织。然而，YY 1高水平过表达的PDAC患者的预后优于低水平过表达的患者。YY 1表达水平与MMP 10表达水平呈统计学负相关，但与MUC 4表达水平无相关性。在体外和体内，YY 1过表达抑制BXPC-3细胞的增殖、侵袭和转移特性，而YY 1敲低则增强。YY 1通过下调MMP 10在MUC 4/ErbB 2/p38/MEF 2C-dependent mechanism.ConclusionsThe本研究表明，YY 1在PDAC中起负性作用，即是一种肿瘤抑制因子，并可能成为PDAC诊断和预后的一个有价值的标志物。
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.
登录
查看更多内容
DOI：
10.1186/bcr1851
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Allouche A;Nolens G;Tancredi A;Delacroix L;Mardaga J;Fridman V;Winkler R;Boniver J;Delvenne P;Begon DY
通讯作者：
Begon DY
影响因子：
3.7
作者：
Jonckheere N;Skrypek N;Merlin J;Dessein AF;Dumont P;Leteurtre E;Harris A;Desseyn JL;Susini C;Frénois F;Van Seuningen I
通讯作者：
Van Seuningen I
DOI：
10.1097/igc.0b013e31821d2525
发表时间：
2011-08
期刊：
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
影响因子：
--
作者：
He G;Wang Q;Zhou Y;Wu X;Wang L;Duru N;Kong X;Zhang P;Wan B;Sui L;Guo Q;Li JJ;Yu L
通讯作者：
Yu L
影响因子：
64.5
作者：
Chang, Shurong;Young, Bryan D.;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
4.3
作者：
Castellano, Giancarlo;Torrisi, Elena;Libra, Massimo
通讯作者：
Libra, Massimo