title: CCR6 is a prognostic marker for overall survival in patients with colorectal cancer, and its overexpression enhances metastasis in vivo.
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.
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Jinlin
authors: J
authors: Liu
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Fang
authors: F
authors: Ke
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zhenyao
authors: Z
authors: Xu
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zhaoyuan
authors: Z
authors: Liu
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Lingyun
authors: L
authors: Zhang
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Sha
authors: S
authors: Yan
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zhe
authors: Z
authors: Wang
authors: Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Hong
authors: H
authors: Wang
authors: 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.
authors: Honglin
authors: H
authors: Wang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C106311:CCR6 protein, human; D034741:RNA, Small Interfering; D054399:Receptors, CCR6; D051057:Proto-Oncogene Proteins c-akt