Oncotarget

Research Papers:

STC2 promotes the epithelial-mesenchymal transition of colorectal cancer cells through AKT-ERK signaling pathways

Bing Chen, Xiao Zeng, Yu He, Xixi Wang, Ziwei Liang, Jingjing Liu, Peng Zhang, Hongxia Zhu, Ningzhi Xu and Shufang Liang _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:71400-71416. https://doi.org/10.18632/oncotarget.12147

Metrics: PDF 1494 views  |   HTML 1442 views  |   ?  


Abstract

Bing Chen1,*, Xiao Zeng1,*, Yu He1, Xixi Wang1, Ziwei Liang1, Jingjing Liu1, Peng Zhang2, Hongxia Zhu1,3, Ningzhi Xu1,3, Shufang Liang1

1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, P.R. China

2Department of Urinary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, P. R. China

3Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, 100034, P. R. China

*These authors contributed equaly to this work

Correspondence to:

Shufang Liang, email: zizi2006@scu.edu.cn

Keywords: stanniocalcin 2, colorectal cancer, epithelial-mesenchymal transition, tumor biomarker

Received: March 26, 2016     Accepted: September 13, 2016     Published: September 20, 2016

ABSTRACT

The STC2 protein involves in carcinogenesis and progression of many cancers. It remains unclear how STC2 regulates the epithelial-mesenchymal transition (EMT) process and colorectal cancer (CRC) development. Here we systematically investigated STC2-activated early occurrence of EMT and CRC cell migration in vitro, clinical associations of STC2 with CRC development and patient survival. The secretion and expression level of STC2 were both greatly increased in EMT cells and CRC cells compared with the normal epithelial NCM460 cells. And the conditioned media from EMT cells stimulated epithelia and colon cancer cells to obtain EMT characteristics. STC2 overexpression promoted CRC cell growth and cell migration in vitro, and STC2 enhanced tumor growth in a mouse CRC-xenograft model. Corresponding to EMT marker expression changes, several critical signaling pathway molecules including pERK, pAKT, PI3K and Ras were remarkably increased either in NCM460 cells transfected with STC2 plasmids or in cells induced with exogenous STC2 protein. However blocking AKT-ERK signaling pathways attenuated STC2-activated EMT process. Furthermore the elevated STC2 expressions were also confirmed in 77 clinical tumor tissues and sera from CRC patients, and the increased STC2 in tumor tissues and sera correlated with tumor pathologic stage and poor survival for CRC patients. In conclusion, STC2 promotes CRC tumorigenesis and EMT progression through activating ERK/MEK and PI3K/AKT signaling pathways. STC2 protein is also a potential tumor biomarker for CRC diagnosis and prognosis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 12147