title: Upregulation of KPNβ1 in gastric cancer cell promotes tumor cell proliferation and predicts poor prognosis.
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.
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Pathology, Nantong First People's Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Qichang
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Oncology, Nantong Tumor Hospital, Nantong, 226361, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Oncology, Nantong Tumor Hospital, Nantong, 226361, Jiangsu, China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathogen Biology, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Oncology, Nantong Tumor Hospital, Nantong, 226361, Jiangsu, China. yangleiylnt@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011485:Protein Binding; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology; D015854:Up-Regulation; D028961:beta Karyopherins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C424166:KPNB1 protein, human; D050794:STAT1 Transcription Factor; D043823:Taxoids; D028961:beta Karyopherins; D000077143:Docetaxel
keywords: Gastric cancer; KPNβ1; Prognosis; Proliferation; Stat1