Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2017; 23(33): 6111-6118
Published online Sep 7, 2017. doi: 10.3748/wjg.v23.i33.6111
Ca2+/calmodulin-dependent protein kinase II regulates colon cancer proliferation and migration via ERK1/2 and p38 pathways
Wei Chen, Ping An, Xiao-Jing Quan, Jun Zhang, Zhong-Yin Zhou, Li-Ping Zou, He-Sheng Luo
Wei Chen, Ping An, Xiao-Jing Quan, Jun Zhang, Zhong-Yin Zhou, He-Sheng Luo, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Ping An, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States
Li-Ping Zou, Department of Education, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Chen W and An P contributed equally to this work; An P designed the research; Chen W, Quan XJ and Zhang J performed the research; Zhou ZY and Zou LP analyzed the data; Luo HS and An P wrote the paper.
Supported by the National Natural Science Foundation of China, No. 81302131.
Institutional review board statement: This study was approved by the Institutional Review Board of Renmin Hospital of Wuhan University.
Conflict-of-interest statement: The authors have no relevant conflicts of interest to disclose.
Data sharing statement: Data can be obtained from the corresponding author.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: He-Sheng Luo, Professor, Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China. xhnk@163.com
Telephone: +86-27-88041911 Fax: +86-27-88041911
Received: February 6, 2017
Peer-review started: February 8, 2017
First decision: May 12, 2017
Revised: June 10, 2017
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: September 7, 2017
Processing time: 212 Days and 21.4 Hours
Abstract
AIM

To investigate the role of calmodulin-dependent protein kinase II (CaMKII) in colon cancer growth, migration and invasion.

METHODS

CaMKII expression in colon cancer and paracancerous tissues was evaluated via immunochemistry. Transcriptional and posttranscriptional levels of CaMKIIin tissue samples and MMP2, MMP9 and TIMP-1 expression in the human colon cancer cell line HCT116 were assessed by qRT-PCR and western blot. Cell proliferation was detected with the MTT assay. Cancer cell migration and invasion were investigated with the Transwell culture system and wound-healing assay.

RESULTS

We first demonstrated that CaMKII was over-expressed in human colon cancers and was associated with cancer differentiation. In the human colon cancer cell line HCT116, the CaMKII-specific inhibitor KN93, but not its inactive analogue KN92, decreased cancer cell proliferation. Furthermore, KN93 also significantly prohibited HCT116 cell migration and invasion. The specific inhibition of ERK1/2 or p38 decreased the proliferation and migration of colon cancer cells.

CONCLUSION

Our findings highlight CaMKII as a potential critical mediator in human colon tumor development and metastasis.

Keywords: Ca2+/calmodulin-dependent protein kinase II; Colon cancer; Proliferation; Migration

Core tip: In the present study, we demonstrated that calmodulin-dependent protein kinase II (CaMKII) was over-expressed in human colon cancers and was associated with cancer differentiation. We investigated the role of CaMKII in human colon cancer proliferation and migration. The results revealed that in the human colon cancer cell line HCT116, the CaMKII-specific inhibitor KN93, but not its inactive analogue KN92, decreased cancer cell proliferation. KN93 also significantly prohibited colon cancer cell migration and invasion. Additionally, we found that ERK1/2 and p38 were the targets of CaMKII regulation. These findings highlight CaMKII as a potential critical mediator in human colon tumor development and metastasis.