CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway
CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway
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DOI：
10.1016/j.intimp.2017.07.018
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发表时间：
2017-10-01
影响因子：
5.6
通讯作者：
Peng, Chun-yan
中科院分区：
文献类型：
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作者：
Lin, Hao-yu;Sun, Shu-ming;Peng, Chun-yan
CCR 10是趋化因子受体亚家族的成员，在多种肿瘤中过表达，在癌症的发生和发展中起着至关重要的作用。然而，CCR 10在乳腺癌中的功能尚不清楚。本研究采用免疫印迹法检测乳腺癌细胞中CCR 10蛋白的表达水平，并采用免疫组化法检测乳腺癌组织中CCR 10的表达。结果显示，乳腺癌MCF 7、BT-474和MDA-MB-231细胞中CCR 10表达升高。CCR 10阳性表达率为70.8%（63/89），且CCR 10的表达水平与被膜浸润、淋巴结转移及肿瘤分期密切相关。CCR 10的配体CCL 27可剂量依赖性地促进乳腺癌细胞的侵袭和迁移，并促进MMP-7的表达和ERK 1/2的激活。通过siRNA转染降低乳腺癌细胞中CCR 10的表达可减弱CCL 27诱导的细胞侵袭力，并抑制MMP-7表达和ERK 1/2激活。此外，阻断ERK 1/2通路抑制了CCL 27/CCR 10促进的乳腺癌细胞的细胞侵袭。总之，这些数据表明，CCL 27/CCR 10相互作用诱导ERK 1/2途径，然后增加MMP-7表达，随后促进乳腺癌细胞的侵袭和迁移。因此，CCR 10可能是乳腺癌细胞侵袭和迁移的关键调节因子。
CCR10, a member of the chemokine receptor subfamily, is overexpressed in several tumors and play a crucial role in cancer development and progression. However, the functions of CCR10 in breast cancer are unknown. Here, we detected the protein levels of CCR10 in breast cancer cells by western blotting, and examined CCR10 expression in breast cancer tissues via immunohistochemical assay. The results showed that CCR10 expression was elevated in breast cancer MCF7, BT-474 and MDA-MB-231 cells. Further, 63 of 89 cases (70.8%) had positive CCR10 staining, and the CCR10 level was closely related to capsular invasion, lymph node metastasis and tumor stage. Moreover, CCL27, the ligand of CCR10, dose-dependently stimulated the invasion and migration of breast cancer cells, and promoted MMP-7 expression and ERK1/2 activation. CCR10 knockdown in breast cancer cells through siRNA transfection attenuated CCL27-induced cell invasiveness, and suppressed MMP-7 expression and ERK1/2 activation. Additionally, blocking the ERK1/2 pathway inhibited the CCL27/CCR10-promoted cell invasion of breast cancer cells. Together, these data suggest that CCL27/CCR10 interaction induces the ERK1/2 pathway, which then increases MMP-7 expresion and subsequently promotes breast cancer cell invasion and migration. Thus, CCR10 may be a key regulator in breast cancer cell invasion and migration.