Open AccessKinesin family member C1 accelerates bladder cancer cell proliferation and induces epithelial–mesenchymal transition via Akt/ GSK 3β signaling
Author(s) -
Xiao Kanghua,
Teng Kai,
Ye Yunlin,
Tan Lei,
Chen Mingkun,
Liang Haitao,
Feng Zihao,
Duan Jinling,
Deng Minhua,
Wei Wensu,
Luo Junhang,
Qin Zike,
Xie Dan
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14126
Subject(s) - epithelial–mesenchymal transition , downregulation and upregulation , cancer research , protein kinase b , cell growth , bladder cancer , pi3k/akt/mtor pathway , biology , metastasis , oncogene , cancer , signal transduction , cell cycle , microbiology and biotechnology , genetics , gene , biochemistry
Abstract Kinesin family member C1 ( KIFC 1) is implicated in the clustering of multiple centrosomes to maintain tumor survival and is thought to be an oncogene in several kinds of cancers. In our experiments, we first performed bioinformatics analysis to investigate the expression levels of KIFC 1 in bladder cancer ( BC ) specimens and normal bladder epitheliums and then, using our samples, verified findings by quantitative real‐time PCR and western blotting assays. All data showed that KIFC 1 was significantly upregulated in BC specimens at both the mRNA and protein levels. Immunohistochemical studies in a cohort of 152 paraffin‐embedded BC tissues displayed that upregulated expression of KIFC 1 clearly correlated with pT status ( P = .014) and recurrent status ( P = .002). Kaplan‐Meier survival analysis and log‐rank test indicated that patients with BC with high KIFC 1 expression had both shorter cancer‐specific survival ( P < .001) and recurrence‐free survival time ( P < .001) than those with low KIFC 1 expression. Furthermore, ectopic downregulation of KIFC 1 weakened BC cell proliferation and migration both in vitro and in vivo, whereas upregulation of KIFC 1 enhanced this in vitro. Overexpression of KIFC 1 phosphorylated GSK 3β and promoted Snail through activating AKT (protein kinase B0) to induce proliferation and epithelial–mesenchymal transition ( EMT ) and, therefore, substantially promoted BC migration and metastasis. Our study revealed an oncogenic role for KIFC 1 to promote BC cell proliferation and EMT via Akt/ GSK 3β signaling; KIFC 1 might be a promising prognostic biomarker as well as a therapeutic target for BC.