Zhu Jia, Wang Yingying, Huang Hua, Yang Qichang, Cai Jing, Wang Qiuhong, Gu Xiaoling, Xu Pan, Zhang Shusen, Li Manhua, Ding Haifang, Yang Lei
Department of Oncology, Nantong Tumor Hospital, Nantong, 226361, Jiangsu, China.
Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
Tumour Biol. 2016 Jan;37(1):661-72. doi: 10.1007/s13277-015-3839-7. Epub 2015 Aug 5.
KPNβ1, also known as importin β, P97, is reported as one of soluble transport factors that mediates transportion of proteins and RNAs between the nucleus and cytoplasm in cellular process. Recent studies show that KPNβ1 is a tumor gene which is highly expressed in several malignant tumors such as ovarian cancer, cervical tumor, neck cancer, and lung cancer via promoting cell proliferation or inhibiting cell apoptotic pathways. However, the the role of KPNβ1 in gastric cancer remains unclear. In this study, Western blot and immunohistochemistrical analyses showed that KPNβ1 was significantly upregulated in clinical gastric cancer specimens compared with adjacent noncancerous tissues. KPNβ1 was positively correlated with tumor grade, Ki-67, and predicted poor prognosis of gastric cancer. More importantly, through starvation-refeeding model, CCK8 assay, flow cytometry, colony formation assays, the vitro studies demonstrated that KPNβ1 promoted proliferation of gastric cancer cells, while KPNβ1 knockdown led to decreased cell proliferation and arrested cell cycle at G1 phase. Furthermore, our results also indicated that KPNβ1 expression could result in docetaxel resistance. And, KPNβ1 could interact with Stat1, contributed to its nucleus import in gastric cancer cells. These findings provided a novel promising therapeutic targets for clinical treatment against human gastric cancer.
KPNβ1,也被称为输入蛋白β、P97,据报道是一种可溶性转运因子,在细胞过程中介导蛋白质和RNA在细胞核与细胞质之间的转运。最近的研究表明,KPNβ1是一种肿瘤基因,通过促进细胞增殖或抑制细胞凋亡途径,在卵巢癌、宫颈癌、头颈癌和肺癌等多种恶性肿瘤中高表达。然而,KPNβ1在胃癌中的作用仍不清楚。在本研究中,蛋白质印迹法和免疫组织化学分析表明,与相邻的非癌组织相比,KPNβ1在临床胃癌标本中显著上调。KPNβ1与肿瘤分级、Ki-67呈正相关,并预示胃癌预后不良。更重要的是,通过饥饿-再喂养模型、CCK8检测、流式细胞术、集落形成试验,体外研究表明KPNβ1促进胃癌细胞增殖,而KPNβ1敲低导致细胞增殖减少并使细胞周期停滞在G1期。此外,我们的结果还表明KPNβ1表达可导致多西他赛耐药。并且,KPNβ1可与Stat1相互作用,促进其在胃癌细胞中的核输入。这些发现为临床治疗人类胃癌提供了一个新的有前景的治疗靶点。