Oncostatin M receptor, positively regulated by SP1, promotes gastric cancer growth and metastasis upon treatment with Oncostatin M
Oncostatin M receptor, positively regulated by SP1, promotes gastric cancer growth and metastasis upon treatment with Oncostatin M
复制标题
制瘤素 M 受体受 SP1 正向调节，在制瘤素 M 治疗后促进胃癌生长和转移
DOI：
10.1007/s10120-019-00934-y
复制
发表时间：
2019-09-01
期刊：
影响因子：
7.4
通讯作者：
Su, Liping
中科院分区：
文献类型：
--
作者：
Yu, Zhenjia;Li, Zhen;Su, Liping
背景抑瘤素M受体（Oncostatin M receptor，OSMR）是白细胞介素6（interleukin 6，IL-6）受体家族的一员，介导抑瘤素M（Oncostatin M，OSM）的信号转导。OSM-OSMR信号传导在炎症和癌症进展中起关键作用。然而，OSM-OSMR在胃癌（GC）中的作用仍然未知。方法采用实时荧光定量PCR（RT-PCR）、免疫组化（IHC）和Western blot检测胃癌组织中OSMR的表达。观察OSM-OSMR对胃癌细胞增殖、迁移、侵袭、上皮-间质转化（EMT）和体内转移的影响。Western blot检测OSM-OSMR信号通路。探讨SP1与OSMR之间的调控机制。结果OSMR在胃癌组织中呈高表达，其表达水平与胃癌患者的年龄、T分期、Lauren分级、淋巴结转移、TNM分期及预后密切相关。OSMR在GC细胞中的表达的敲低显著抑制细胞增殖、迁移、侵袭和体外EMT，以及由OSM诱导的体内肿瘤发生和腹膜转移。OSM-OSMR介导的这些作用依赖于STAT 3/FAK/Src信号通路的激活。SP1可与人OSMR基因启动子区-255 ~-246 bp结合，并可调控OSMR在胃癌细胞中的过表达。结论OSM-OSMR通过激活STAT 3/FAK/Src信号通路参与胃癌的发生发展，OSMR受SP1的转录激活。
Background Oncostatin M receptor (OSMR) is a member of the interleukin 6 (IL-6) receptor family that transduces signaling events of Oncostatin M (OSM). OSM-OSMR signaling plays a key role in inflammation and cancer progression. However, the role of OSM-OSMR in gastric cancer (GC) is still unknown. Methods OSMR expression in GC was determined by real-time PCR (RT-PCR), immunohistochemistry (IHC) and Western blot. The effects of OSM-OSMR on GC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo were examined. The pathways underlying OSM-OSMR signaling were explored by Western blot. Regulatory mechanism between SP1 and OSMR was explored in vitro. Results OSMR was highly expressed in GC tissues and its expression level was closely associated with age, T stage, Lauren classification, lymph node metastasis, TNM stage and worse prognosis of patients with GC. Knockdown of OSMR expression in GC cells significantly inhibited cell proliferation, migration, invasion, and EMT in vitro, as well as tumorigenesis and peritoneal metastasis in vivo induced by OSM. These effects mediated by OSM-OSMR were dependent on the activation of STAT3/FAK/Src signaling. SP1 could bind to the promoter region of human OSMR gene from - 255 to - 246 bp, and transcriptionally regulated OSMR overexpression in GC cells. Conclusions OSM-OSMR contributes to GC progression through activating STAT3/FAK/Src signaling, and OSMR is transcriptionally activated by SP1.