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High Kpnβ1 expression promotes non-small cell lung cancer proliferation and chemoresistance via the PI3-kinase/AKT pathway.
Tissue & Cell 2018 April
Karyopherin β1 (Kpnβ1), also known as importin-β, is part of the karyopherin superfamily of nuclear transport proteins. Kpnβ1 is an oncogene that is overexpressed in various human cancers. Recent studies have showed that Kpnβ1 is one of the leading causes of cancer-related deaths in the world. However, the role of Kpnβ1 in non-small cell lung cancer (NSCLC) remains uncertain. In this study, we used western blotting to show that Kpnβ1 expression is higher in lung-cancer tissues and cells, and immunohistochemistry analysis revealed that Kpnβ1 was significantly associated with the clinicopathological features of NSCLC. Kaplan-Meier analysis showed that elevated Kpnβ1 expression correlated with a poor prognosis in NSCLC patients. Serum starvation-refeeding experiments and Kpnβ1-shRNA transfection assays revealed that elevated Kpnβ1 expression promoted cell proliferation and reduced sensitivity to cis-diamminedichloroplatinum. Immunoprecipitation assays showed that Kpnβ1 interacts with PI3 K to activate the PI3-kinase/AKT pathway, leading to enhanced cell survival and drug resistance in NSCLC cells. Collectively, our findings suggest that Kpnβ1 plays a significant role in NSCLC progression and chemoresistance. Our study provides new insights for targeted therapy to treat NSCLC.
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