CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition

• Type of Material: Article
• Authors: Neeraj Kapur, Morehouse School of Medicine; Hina Mir, Morehouse School of Medicine; Clarence E Clark, Morehouse School of Medicine; Uma Krishnamurti, Emory University; Derrick J Beech, Morehouse School of Medicine; James W Lillard, Morehouse School of Medicine; Shailesh Singh, Morehouse School of Medicine
• Language: English
• Date: 2016-06-14
• Publisher: Cancer Research UK
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2016 Cancer Research UK
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/bjc.2016.113
• Title of Journal or Parent Work: British Journal of Cancer
• ISSN: 0007-0920
• Volume: 114
• Issue: 12
• Start Page: 1343
• End Page: 1351
• Grant/Funding Information: This study was supported in part by the funds (R21 CA169716, SC1 CA180212, U54 CA118638 and UO1 CA179701) from NCI and Morehouse School of Medicine flow cytometry core (G12 MD007602).
• Keywords: Oncology; METALLOPROTEINASE EXPRESSION; BREAST-CANCER; II COLORECTAL-CANCER; colon cancer; Life Sciences & Biomedicine; migration and invasion; SIGNALING PATHWAY; TRANSCRIPTION FACTOR SNAIL; metastasis; CCR6; Science & Technology; PROSTATE-CANCER; CELL-MIGRATION; E-CADHERIN EXPRESSION; CCL20; EMT; CHEMOKINE RECEPTOR CCR6; TUMOR PROGRESSION
• Research Categories: Biology, Molecular; Health Sciences, Oncology

Abstract

Background:Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway.Methods:Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20.Results:CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, β-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential.Conclusions:Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.