CST4的过表达通过激活ELFN2信号通路促进胃癌侵袭性。
Overexpression of CST4 promotes gastric cancer aggressiveness by activating the ELFN2 signaling pathway.
作者信息
Zhang Yi Qiang, Zhang Jing Jing, Song Hong Jie, Li Da Wei
机构信息
Department of Gastroenterology, Zhumadian Central Hospital of Henan ProvinceZhumadian, China.
Department of Laboratory Medicine, The Third Hospital of Xinxiang Medical UniversityXinxiang, China.
出版信息
Am J Cancer Res. 2017 Nov 1;7(11):2290-2304. eCollection 2017.
Gastric cancer is one of the most lethal malignancies of gastrointestinal cancer and its prognosis remains dismal because of the paucity of effective therapeutic targets. Here, we show that cystatin 4 (CST4) is markedly upregulated in gastric cancer cell lines and clinical tissues. Ectopic expression of CST4 in gastric cancer cells promoted proliferation, migration, and invasion of gastric cancer cells in vitro. Furthermore, CST4 overexpression significantly promoted the tumorigenicity of gastric cancer cells in vivo, whereas silencing endogenous CST4 caused an opposite outcome. In addition, extracellular leucine rich repeat and fibronectin type III domain containing 2 (ELFN2) was identified as a downstream target of CST4 in gastric cancer cells and was positively correlated with ELFN2 expression in gastric cancer tissues. Finally, we demonstrated that CST4 enhanced gastric cancer aggressiveness by regulating ELFN2 signaling. Together, our results provide new evidence that CST4 overexpression promotes the progression of gastric cancer and might represent a novel therapeutic target for its treatment.
胃癌是胃肠道癌症中最致命的恶性肿瘤之一，由于缺乏有效的治疗靶点，其预后仍然很差。在这里，我们表明胱抑素4（CST4）在胃癌细胞系和临床组织中显著上调。CST4在胃癌细胞中的异位表达促进了胃癌细胞在体外的增殖、迁移和侵袭。此外，CST4过表达在体内显著促进了胃癌细胞的致瘤性，而沉默内源性CST4则产生相反的结果。此外，富含亮氨酸重复序列和III型纤连蛋白结构域的细胞外蛋白2（ELFN2）被确定为胃癌细胞中CST4的下游靶点，并且与胃癌组织中ELFN2的表达呈正相关。最后，我们证明CST4通过调节ELFN2信号增强了胃癌的侵袭性。总之，我们的结果提供了新的证据，即CST4过表达促进胃癌进展，可能是其治疗的一个新的治疗靶点。
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