Upregulation of KPNβ1 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis

作者：Zhu, Jia; Wang, Yingying; Huang, Hua; Yang, Qichang; Cai, Jing; Wang, Qiuhong; Gu, Xiaoling; Xu, Pan; Zhang, Shusen; Li, Manhua; Ding, Haifang; Yang, Lei^*

来源：Tumor Biology, 2016, 37(1): 661-672.

DOI：10.1007/s13277-015-3839-7

• Gastric cancer
• KPN beta 1
• Proliferation
• Prognosis
• Stat1

KPN beta 1, also known as importin beta, 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 KPN beta 1 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 KPN beta 1 in gastric cancer remains unclear. In this study, Western blot and immunohistochemistrical analyses showed that KPN beta 1 was significantly upregulated in clinical gastric cancer specimens compared with adjacent noncancerous tissues. KPN beta 1 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 KPN beta 1 promoted proliferation of gastric cancer cells, while KPN beta 1 knockdown led to decreased cell proliferation and arrested cell cycle at G1 phase. Furthermore, our results also indicated that KPN beta 1 expression could result in docetaxel resistance. And, KPN beta 1 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.

• 出版日期2016-1
• 单位南通市肿瘤医院; 南通大学