ESE3 Inhibits Pancreatic Cancer Metastasis by Upregulating E-Cadherin.
ESE3 Inhibits Pancreatic Cancer Metastasis by Upregulating E-Cadherin.
复制标题
ESE3 通过上调 E-钙粘蛋白抑制胰腺癌转移
DOI：
10.1158/0008-5472.can-16-2170
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发表时间：
2017-02-15
期刊：
影响因子：
11.2
通讯作者：
Hao J
中科院分区：
文献类型：
--
作者：
Zhao T;Jiang W;Wang X;Wang H;Zheng C;Li Y;Sun Y;Huang C;Han ZB;Yang S;Jia Z;Xie K;Ren H;Hao J
ETS 家族转录因子 ESE3 是许多上皮组织分化和发育程序的关键元件。在这里，我们报道了它在胰腺癌中作为肿瘤抑制因子的作用。我们观察到，与邻近的正常胰腺组织相比，胰腺导管腺癌 (PDAC) 中 ESE3 的表达显着降低。 PDAC 中 ESE3 表达的降低与淋巴结转移和血管侵袭的增加以及患者无复发生存率和总生存率的降低密切相关。在功能实验中，在原位小鼠模型中，下调 ESE3 的表达可促进 PDAC 细胞的运动性和侵袭性以及转移。 PDAC 细胞系、原位小鼠模型和人类 PDAC 标本的机制研究表明，ESE3 通过直接上调 E-钙粘蛋白转录水平的表达来抑制 PDAC 转移。总的来说，我们的结果表明 ESE3 通过上调 E-钙粘蛋白作为 PDAC 进展和转移的负调节因子。癌症研究； 77(4)； 874-85。 ©2016 AACR。
The ETS family transcription factor ESE3 is a crucial element in differentiation and development programs for many epithelial tissues. Here we report its role as a tumor suppressor in pancreatic cancer. We observed drastically lower ESE3 expression in pancreatic ductal adenocarcinomas (PDAC) compared with adjacent normal pancreatic tissue. Reduced expression of ESE3 in PDAC correlated closely with an increase in lymph node metastasis and vessel invasion and a decrease in relapse-free and overall survival in patients. In functional experiments, downregulating the expression of ESE3 promoted PDAC cell motility and invasiveness along with metastasis in an orthotopic mouse model. Mechanistic studies in PDAC cell lines, the orthotopic mouse model, and human PDAC specimens demonstrated that ESE3 inhibited PDAC metastasis by directly upregulating E-cadherin expression at the level of its transcription. Collectively, our results establish ESE3 as a negative regulator of PDAC progression and metastasis by enforcing E-cadherin upregulation. Cancer Res; 77(4); 874-85. ©2016 AACR.