title: Interleukin-17 induces CC chemokine receptor 6 expression and cell migration in colorectal cancer cells.
abstract: The CC chemokine receptor 6 (CCR6) and its ligand CCL20 are involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. In addition, interleukin-17 (IL-17), produced by a T cell subset named "Th17," has been identified as an important player in inflammatory responses, and has emerged as a mediator in inflammation-associated cancer. However, the relevance of IL-17 in the development and progression of CRC still remains to be explored. This study aimed to investigate the effect of IL-17 on the cell migration of CRC cells. Human CRC HCT-116 cells were used to study the effect of IL-17 on CCR6 expression and cell migration in CRC cells. IL-17 treatment induced migration of HCT-116 cells across the Boyden chamber membrane and increased the expression level of the CCR6. Inhibition of CCR6 by small interfering RNA (siRNA) and neutralizing antibody inhibited IL-17-induced cell migration. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK and p38 pathways are critical for IL-17-induced CCR6 expression and cell migration. Promoter activity and transcription factor ELISA assays showed that IL-17 increased NF-κB-DNA binding activity in HCT-116 cells. Inhibition of NF-κB activation by specific inhibitors and siRNA blocked the IL-17-induced CCR6 expression. Our findings support the hypothesis that CCR6 up-regulation stimulated by IL-17 may play an active role in CRC cell migration.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Chin
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Chen
authors.forename: Hsing-Chun
authors.initials: HC
authors.lastname: Kuo
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Shi
authors.forename: Meng Chiao
authors.initials: MC
authors.lastname: Hsieh
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Kuo
authors.forename: Shui-Yi
authors.initials: SY
authors.lastname: Tung
authors.forename: Kam-Fai
authors.initials: KF
authors.lastname: Lee
authors.forename: Wen-Shih
authors.initials: WS
authors.lastname: Huang
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D015179:Colorectal Neoplasms; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; D020381:Interleukin-17; D016328:NF-kappa B; D054399:Receptors, CCR6; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases