Shanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; Shanghai Institute of Digestive Surgery, Shanghai, PR China.
Shanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Biochim Biophys Acta Mol Basis Dis. 2018 Feb;1864(2):387-397. doi: 10.1016/j.bbadis.2017.10.033. Epub 2017 Oct 31.
Chemokines and chemokine receptors play an important role in tumorigenesis. Angiogenesis is a vital part of the occurrence, development and metastasis of cancer. CCR6 is an important factor during tumor progression; however, its function in tumor angiogenesis is not fully understood. In our study, we found that CCR6 was significantly overexpressed in colorectal cancer (CRC) tissues and predicted a poor prognosis in CRC patients. We then verified the function of CCR6 on tumor angiogenesis in vivo and in vitro. We observed that silencing CCR6 could decrease angiogenesis by inhibiting the proliferation and migration of human umbilical vein endothelial cells (HUVECs), whereas overexpression of CCR6 can promote angiogenesis. Additionally, we investigated the molecular mechanisms and demonstrated that activation of the AKT/NF-κB pathway maybe involved in CCR6-mediated tumor angiogenesis, which was able to promote the secretion of vascular endothelial growth factor A (VEGF-A). In conclusion, CCR6 facilitates tumor angiogenesis via the AKT/NF-κB/VEGF pathway in colorectal cancer. CCR6 inhibition may be a novel option for anti-vascular treatment in CRC.
趋化因子及其受体在肿瘤发生中发挥重要作用。血管生成是癌症发生、发展和转移的重要组成部分。CCR6 是肿瘤进展过程中的一个重要因素，但它在肿瘤血管生成中的作用尚不完全清楚。在我们的研究中，我们发现 CCR6 在结直肠癌（CRC）组织中显著过表达，并预测 CRC 患者预后不良。然后，我们在体内和体外验证了 CCR6 对肿瘤血管生成的功能。我们观察到沉默 CCR6 可以通过抑制人脐静脉内皮细胞（HUVEC）的增殖和迁移来减少血管生成，而 CCR6 的过表达可以促进血管生成。此外，我们研究了分子机制，并证明 AKT/NF-κB 通路的激活可能参与了 CCR6 介导的肿瘤血管生成，这可以促进血管内皮生长因子 A（VEGF-A）的分泌。总之，CCR6 通过 AKT/NF-κB/VEGF 通路促进结直肠癌中的肿瘤血管生成。CCR6 抑制可能是 CRC 抗血管治疗的新选择。
