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

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Tumor Biology

Abstract

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.81302285, No. 81402015); the Natural Science Foundation of Nantong University (No.12Z009).

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    Authors and Affiliations

    1. Department of Oncology, Nantong Tumor Hospital, Nantong, 226361, Jiangsu, China

      Jia Zhu, Jing Cai, Qiuhong Wang & Lei Yang

    2. Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China

      Jia Zhu, Yingying Wang, Xiaoling Gu, Pan Xu, Shusen Zhang, Manhua Li & Haifang Ding

    3. Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Hua Huang

    4. Department of Pathology, Nantong First People’s Hospital, Nantong, 226001, Jiangsu, China

      Qichang Yang

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    1. Jia Zhu
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    Correspondence to Lei Yang.

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    Jia Zhu and Yingying Wang contributed equally to this work.

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    Zhu, J., Wang, Y., Huang, H. et al. Upregulation of KPNβ1 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis. Tumor Biol. 37, 661–672 (2016). https://doi.org/10.1007/s13277-015-3839-7

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    • DOI: https://doi.org/10.1007/s13277-015-3839-7

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