HIC1 attenuates invasion and metastasis by inhibiting the IL-6/STAT3 signalling pathway in human pancreatic cancer
HIC1 attenuates invasion and metastasis by inhibiting the IL-6/STAT3 signalling pathway in human pancreatic cancer
复制标题
HIC1通过抑制人胰腺癌中的IL-6/STAT3信号通路来减弱侵袭和转移
DOI：
10.1016/j.canlet.2016.04.013
复制
发表时间：
2016-07-01
期刊：
影响因子：
9.7
通讯作者：
Hu, Guoyong
中科院分区：
文献类型：
--
作者：
Hu, Bin;Zhang, Kundong;Hu, Guoyong
癌症中的高甲基化1（Hypermethylated in cancer 1，HM 1）是一种肿瘤抑制基因，在许多人类癌症中经常缺失或表观遗传学沉默。然而，在胰腺癌中，尤其是在肿瘤的侵袭和转移中，RISK 1的分子功能尚未完全阐明。我们的目的是阐明胰腺癌与肿瘤的临床相关性及其影响侵袭和转移的机制。在胰腺癌患者癌组织和胰腺癌细胞系中，BMP 1表达下调。组织微阵列分析表明，阴性表达预示着晚期病理阶段和较差的患者生存期。此外，在体外和体内实验中，BMP 1均能抑制胰腺癌细胞的侵袭和转移。最后，STAT 1通过与STAT 3结合并相互作用以阻碍其DNA结合能力而抑制STAT 3靶基因的表达，包括c-Myc、VEGF、CyclinD 1、MMP 2和MMP 9，但不影响STAT 3和p-STAT 3的蛋白水平。因此，BMP 1似乎起着STAT 3抑制剂的作用，可能是癌症研究和开发胰腺癌最佳治疗方法的一个有前途的靶点。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Hypermethylated in cancer 1 (HIC1) is a tumour suppressor gene that is frequently deleted or epigenetically silenced in many human cancers. However, the molecular function of HIC1 in pancreatic cancer has not been fully elucidated, especially in cancer invasion and metastasis. We aimed to clarify the clinical relevance of HIC1 and human pancreatic cancer and the mechanism of its effect on invasion and metastasis. HIC1 was downregulated in pancreatic cancer patient cancer tissue and pancreatic cancer cell lines. A tissue microarray analysis demonstrated that negative HIC1 expression predicted advanced pathological stages and worse patient survival. In addition, HIC1 inhibited the invasion and metastasis of pancreatic cancer cells both in vitro and in vivo. Finally, HIC1 repressed the expression of STAT3 target genes, including c-Myc, VEGF, CyclinD1, MMP2 and MMP9, by binding and interacting with STAT3 to impede its DNA-binding ability but without affecting the protein levels of STAT3 and p-STAT3. Therefore, HIC1 appears to function as a STAT3 inhibitor and may be a promising target for cancer research and for the development of an optimal treatment approach for pancreatic cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.