KIF15 knockdown suppresses gallbladder cancer development
Gallbladder cancer (GBC) is commonly regarded as one of the most lethal malignant tumor types with poor prognosis. Kinesin family member 15 (KIF15) is reported to be tightly related with progression of multiple cancer types which, however, has not been clarified in GBC so far. KIF15 was significantl...
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Elsevier
2021
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oai:doaj.org-article:cf3c3e3d2112480fb374c7b7d17e44c42021-11-14T04:28:29ZKIF15 knockdown suppresses gallbladder cancer development0171-933510.1016/j.ejcb.2021.151182https://doaj.org/article/cf3c3e3d2112480fb374c7b7d17e44c42021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0171933521000339https://doaj.org/toc/0171-9335Gallbladder cancer (GBC) is commonly regarded as one of the most lethal malignant tumor types with poor prognosis. Kinesin family member 15 (KIF15) is reported to be tightly related with progression of multiple cancer types which, however, has not been clarified in GBC so far. KIF15 was significantly up-regulated in clinical GBC tissues compared with that in para-carcinoma tissues and the expression level was also correlated with tumor malignancies. In addition to tissues, GBC cells also exhibited a high expression abundance of KIF15. After down-regulating KIF15 via lentiviral transfection, GBC cell proliferation and migration were both inhibited, while cell apoptosis was promoted markedly. Likewise, silencing KIF15 significantly interfered the growth of nude mouse xenografts. Our experiments in GBC cell lines also demonstrated that KIF15 overexpression accelerated cell proliferation but lessened cell apoptosis in both GBC-SD and SGC-996 cells. Further investigation of the mechanism occurring in GBC inhibition mediated by KIF15 knockdown revealed that KIF15 deficiency led to decreased activity of several signaling pathways (TNF, PI3K/AKT and MAPK), a reduction of CDK6 expression regulated by enhanced p21, and HSP60 absence. Following the treatment of shCtrl- and shKIF15-transfected cells with AKT activator, we found that anti-tumor effects resulting from KIF15 deficiency could be relieved by AKT activator in both experimental cells. Overall, for the first time, we demonstrated that KIF15 was overexpressed in GBC and displayed a close relationship between KIF15 levels and GBC clinical stages. Furthermore, low expression of KIF15 resulted in obvious anti-tumor effects.Jun WangDandan WangZhewei FeiDongxu FengBo ZhangPingfa GaoGangfeng HuWenbing LiXia HuangDawei ChenXinde DingWei WuElsevierarticleKIF15Gallbladder cancerMolecular targetApoptosisProliferationMigrationCytologyQH573-671ENEuropean Journal of Cell Biology, Vol 100, Iss 7, Pp 151182- (2021) |
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KIF15 Gallbladder cancer Molecular target Apoptosis Proliferation Migration Cytology QH573-671 |
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KIF15 Gallbladder cancer Molecular target Apoptosis Proliferation Migration Cytology QH573-671 Jun Wang Dandan Wang Zhewei Fei Dongxu Feng Bo Zhang Pingfa Gao Gangfeng Hu Wenbing Li Xia Huang Dawei Chen Xinde Ding Wei Wu KIF15 knockdown suppresses gallbladder cancer development |
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Gallbladder cancer (GBC) is commonly regarded as one of the most lethal malignant tumor types with poor prognosis. Kinesin family member 15 (KIF15) is reported to be tightly related with progression of multiple cancer types which, however, has not been clarified in GBC so far. KIF15 was significantly up-regulated in clinical GBC tissues compared with that in para-carcinoma tissues and the expression level was also correlated with tumor malignancies. In addition to tissues, GBC cells also exhibited a high expression abundance of KIF15. After down-regulating KIF15 via lentiviral transfection, GBC cell proliferation and migration were both inhibited, while cell apoptosis was promoted markedly. Likewise, silencing KIF15 significantly interfered the growth of nude mouse xenografts. Our experiments in GBC cell lines also demonstrated that KIF15 overexpression accelerated cell proliferation but lessened cell apoptosis in both GBC-SD and SGC-996 cells. Further investigation of the mechanism occurring in GBC inhibition mediated by KIF15 knockdown revealed that KIF15 deficiency led to decreased activity of several signaling pathways (TNF, PI3K/AKT and MAPK), a reduction of CDK6 expression regulated by enhanced p21, and HSP60 absence. Following the treatment of shCtrl- and shKIF15-transfected cells with AKT activator, we found that anti-tumor effects resulting from KIF15 deficiency could be relieved by AKT activator in both experimental cells. Overall, for the first time, we demonstrated that KIF15 was overexpressed in GBC and displayed a close relationship between KIF15 levels and GBC clinical stages. Furthermore, low expression of KIF15 resulted in obvious anti-tumor effects. |
format |
article |
author |
Jun Wang Dandan Wang Zhewei Fei Dongxu Feng Bo Zhang Pingfa Gao Gangfeng Hu Wenbing Li Xia Huang Dawei Chen Xinde Ding Wei Wu |
author_facet |
Jun Wang Dandan Wang Zhewei Fei Dongxu Feng Bo Zhang Pingfa Gao Gangfeng Hu Wenbing Li Xia Huang Dawei Chen Xinde Ding Wei Wu |
author_sort |
Jun Wang |
title |
KIF15 knockdown suppresses gallbladder cancer development |
title_short |
KIF15 knockdown suppresses gallbladder cancer development |
title_full |
KIF15 knockdown suppresses gallbladder cancer development |
title_fullStr |
KIF15 knockdown suppresses gallbladder cancer development |
title_full_unstemmed |
KIF15 knockdown suppresses gallbladder cancer development |
title_sort |
kif15 knockdown suppresses gallbladder cancer development |
publisher |
Elsevier |
publishDate |
2021 |
url |
https://doaj.org/article/cf3c3e3d2112480fb374c7b7d17e44c4 |
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