CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo

Jinlin Liu; Fang Ke; Zhenyao Xu; Zhaoyuan Liu; Lingyun Zhang; Sha Yan; Zhe Wang; Hong Wang; Honglin Wang

doi:10.1371/journal.pone.0101137

CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo

PLoS One. 2014 Jun 30;9(6):e101137. doi: 10.1371/journal.pone.0101137. eCollection 2014.

Authors

Jinlin Liu¹, Fang Ke¹, Zhenyao Xu¹, Zhaoyuan Liu¹, Lingyun Zhang¹, Sha Yan¹, Zhe Wang¹, Hong Wang¹, Honglin Wang²

Affiliations

¹ Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

The chemokine receptor CCR6 has been recently shown to be associated with colorectal cancer (CRC) progression. However, the direct evidence for whether CCR6 in tumors is a prognostic marker for the survival of patients with CRC and whether it plays a critical role in CRC metastasis in vivo is lacking. Here we show that the levels of CCR6 were upregulated in CRC cell lines and primary CRC clinical samples. CCR6 upregulation was closely correlated with disease stages and the survival time of CRC patients. Knockdown of CCR6 inhibited the migration of CRC cells in vitro. Overexpression of CCR6 in CRC cells increased their proliferation, migration, and colony formation in vitro and promoted their metastatic potential in vivo. CCR6 activated Akt signaling, upregulated metastasis genes and downregulated metastasis suppressor genes. Selective targeting of CCR6 in tumors dramatically inhibited the growth of CRC in mice. Thus, the tumor expression of CCR6 plays a critical role in CRC metastasis, upregulated CCR6 predicts poor survival in CRC patients, and targeting CCR6 expression in tumors may be a potential therapeutic strategy for CRC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers, Tumor / metabolism
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism*
Colorectal Neoplasms / pathology*
Disease Progression
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Male
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Metastasis
Prognosis
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / metabolism
Receptors, CCR6 / genetics
Receptors, CCR6 / metabolism*
Signal Transduction / genetics
Survival Analysis
Up-Regulation

Substances

Biomarkers, Tumor
CCR6 protein, human
RNA, Small Interfering
Receptors, CCR6
Proto-Oncogene Proteins c-akt

Grants and funding

This work is supported by grants from National Natural Science Foundation of China and 973 Program (No: 91029730, No: 81202304, No: 2012CB917100, No: 2010CB529700 and No: 30972787), by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning, by the Science and Technology Commission of Shanghai Municipality (No: 09140902600), by the Leading Academic Discipline Project of the Shanghai Municipal Education Commission (No: J50208 and No: J50207), by Shanghai Pujiang Program (No: 10PJ407300), and by Shanghai Committee of Science and Technology (11DZ2260200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.