Chen Dehu, Liu Guiyuan, Xu Ning, You Xiaolan, Zhou Haihua, Zhao Xiaojun, Liu Qinghong
Cell Physiol Biochem. 2017;42(3):1025-1036. doi: 10.1159/000478685. Epub 2017 Jun 28.
BACKGROUND/AIMS: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis.
ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed.
The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1.
The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.
背景/目的：胃癌（GC）是一种常见的致命性恶性肿瘤，已发现AMP激活的蛋白激酶相关激酶5（ARK5）在某些类型的癌症中促进癌症转移。在本研究中，我们探讨了ARK5在胃癌侵袭和转移中的作用。
通过免疫组织化学和蛋白质印迹法检测胃癌标本中ARK5和上皮-间质转化（EMT）相关标志物。还采用了其他方法，包括将针对ARK5的稳定转染导入SGC7901和AGS细胞、蛋白质印迹法、体外迁移和侵袭试验以及体内裸鼠致瘤性试验。
结果表明，ARK5表达增加，且与胃癌患者的转移、EMT相关标志物及不良预后呈正相关。敲低ARK5表达通过调节EMT显著抑制胃癌细胞的侵袭和转移，而非体外和体内的增殖。敲低胃癌细胞中ARK5的表达导致mTOR/p70S6k信号、Slug和SIP1的下调。
ARK5表达升高与癌症转移和患者生存密切相关，它似乎通过EMT改变以及mTOR/p70S6k信号、Slug和SIP1的改变在胃癌细胞迁移和侵袭中发挥作用，从而为胃癌提供了一个潜在的治疗靶点。
