KIFC1 overexpression promotes prostate cancer cell survival and proliferation in vitro by clustering of amplified centrosomes via interaction with Centrin 2  

作　　者：ANZANA PARVIN BANG-HONG WEI SHUANG-LI HAO WAN-XI YANG FU-QING TAN 

机构地区：[1]The Sperm Laboratory,College of Life Sciences,Zhejiang University,Hangzhou,310058,China [2]The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou,310003,China [3]Department of Biotechnology and Genetic Engineering,Faculty of Biological Sciences,Islamic University,Kushtia,7003,Bangladesh

出　　处：《BIOCELL》2021年第5期1369-1391,共23页生物细胞（英文）

基　　金：Natural Science Foundation of Zhejiang Province,China(No.LY20H040010).

摘　　要：Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of cancer cells,but this phenomenon remains obscure in prostate cancer(PCa).The present study demonstrated that PCa cells showed centrosome amplification and clustering during interphase and mitosis,respectively.KIFC1 is highly expressed in PCa cells and tumor tissues of prostatic adenocarcinoma(PAC)patients.Up-regulation of KIFC1 facilitated the PCa cell survival in vitro by ensuring bipolar mitosis through clustering the multiple centrosomes,suggesting centrosome clustering could be a leading cause of prostate carcinogenesis.Conversely,the silencing of KIFC1 resulted in normal centrosome number or multipolar mitosis by inhibiting the clustering of amplified centrosomes in PCa cells.Besides,knockdown of KIFC1 by RNAi in PCa cells reduced cancer cell survival,and proliferation.KIFC1 interacted with centrosome structural protein Centrin 2 in clustering of amplified centrosomes in PCa cells to ensure the bipolar mitotic spindle formation.Knockdown of Centrin 2 in PCa cells inhibited the centrosome amplification and clustering.Moreover,up-regulated KIFC1 promotes PCa cell proliferation via progression of cell cycle possibly through aberrant activation of cyclin dependent kinase 1(Cdk1).Therefore,KIFC1 can be a prognostic marker and therapeutic target of PCa for inhibiting the cancer cell proliferation.

关 键 词：KIFC1 Centrosome clustering Centrosome amplification Prostate cancer 

分 类 号：R73[医药卫生—肿瘤]