Oncotarget

Research Papers:

Involvement of Polo-like kinase 1 (Plk1) in quiescence regulation of cancer stem-like cells of the gastric cancer cell lines

Lin Zhu, Sheng Xing, Li Zhang, Jian-Min Yu, Cheng Lin and Wei-Jun Yang _

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

Oncotarget. 2017; 8:37633-37645. https://doi.org/10.18632/oncotarget.16839

Metrics: PDF 706 views  |   HTML 1052 views  |   ?  


Abstract

Lin Zhu1, Sheng Xing1, Li Zhang1, Jian-Min Yu1, Cheng Lin1 and Wei-Jun Yang1

1College of Life Sciences, Zhejiang University, Hangzhou 310058, People’s Republic of China

Correspondence to:

Wei-Jun Yang, email: w_jyang@zju.edu.cn

Keywords: PLK1, RSK1, cancer stem cell, quiescence, drug and radiation resistance

Received: September 28, 2016     Accepted: March 14, 2017     Published: April 05, 2017

ABSTRACT

Cancer stem cells (CSCs) have been hypothesized to initiate tumor growth and be resistant to chemoradiotherapy, and these processes appear to be closely related to CSC quiescence. Here, a CSC-like cell population with a high level of CD44 expression was obtained from the human gastric cancer cell lines MKN45 and MKN74. Using a PKH26-labeling retention assay, quiescent CSC-like cells with low levels of Ki67 and PCNA expression were found in spheres formed in serum-free medium, and exhibited resistance to drug and radiation treatments. Polo-like kinase 1 (Plk1) and ribosomal S6 kinase 1 (RSK1) were silenced in the quiescent CSC-like cells. The Plk1-specific inhibitors inhibited the activation of RSK1 and induced quiescence in the CSC-like cells, but increased RSK1 activity and resulted in apoptosis in non-CSCs. Furthermore, RSK1 silencing by inhibitors activated Plk1 and had no effect on the growth of spheres in the CSC-like cells, but did not affect phosphorylation of Plk1 and led to decreased proliferation in non-CSCs. Our results showed that Plk1 and RSK1 play important roles in the conversion of CSCs between active and quiescent states.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 16839