title: CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kapur
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Hina
authors.initials: H
authors.lastname: Mir
authors.affiliation: Department of Surgery, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Clarence E
authors.initials: CE
authors.lastname: Clark Iii
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Krishnamurti
authors.affiliation: Department of Surgery, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Beech
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Lillard
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Singh
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D054418:Chemokine CCL20 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D054399:Receptors, CCR6 / Q000096:biosynthesis*; D015398:Signal Transduction
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D054399:Receptors, CCR6