Liu Jinlin, Ke Fang, Xu Zhenyao, Liu Zhaoyuan, Zhang Lingyun, Yan Sha, Wang Zhe, Wang Hong, Wang Honglin
Shanghai Institute of Immunology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
PLoS One. 2014 Jun 30;9(6):e101137. doi: 10.1371/journal.pone.0101137. eCollection 2014.
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.
趋化因子受体CCR6最近被证明与结直肠癌（CRC）进展相关。然而，肿瘤中的CCR6是否为CRC患者生存的预后标志物以及它在体内CRC转移中是否起关键作用，目前仍缺乏直接证据。在此我们表明，CCR6水平在CRC细胞系和原发性CRC临床样本中上调。CCR6上调与疾病分期及CRC患者的生存时间密切相关。敲低CCR6可在体外抑制CRC细胞迁移。在CRC细胞中过表达CCR6可增加其在体外的增殖、迁移及集落形成，并在体内促进其转移潜能。CCR6激活Akt信号通路，上调转移基因并下调转移抑制基因。在肿瘤中选择性靶向CCR6可显著抑制小鼠体内CRC的生长。因此，CCR6的肿瘤表达在CRC转移中起关键作用，CCR6上调预示CRC患者生存不良，靶向肿瘤中的CCR6表达可能是CRC的一种潜在治疗策略。
