CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway

• Published in: International immunopharmacology 2017-10, Vol.51, p.124-130
• Main Authors: Lin, Hao-yu, Sun, Shu-ming, Lu, Xiao-feng, Chen, Ping-ying, Chen, Chun-fa, Liang, Wei-quan, Peng, Chun-yan
• Format: Article
• Language: English
• Subjects: Activation; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer; Carcinogenesis; CCL27; CCR10; Cell adhesion & migration; Cell Movement; Chemokine CCL27 - metabolism; ERK1/2; Extracellular signal-regulated kinase; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Invasion; Invasiveness; Leukocyte migration; Lymph nodes; Lymphatic Metastasis; MAP Kinase Signaling System; Matrilysin; Matrix Metalloproteinase 7 - metabolism; MCF-7 Cells; Metastases; Middle Aged; Migration; Neoplasm Staging; Proteins; Receptors, CCR10 - genetics; Receptors, CCR10 - metabolism; RNA, Small Interfering - genetics; Signal transduction; Signaling; siRNA; Studies; Tissues; Transfection; Tumors; Western blotting
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.07.018

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. •CCR10 expression was upregulated in breast cancer cells and tissues.•CCL27/CCR10 axis promoted breast cancer cell invasion and migration.•CCL27/CCR10 axis increased MMP-7 expression and induced ERK1/2 activation.•ERK1/2 pathway was required for CCL27/CCR10-mediated cell invasion and migration.