Open AccessCCR7 mediates human breast cancer cell invasion, migration by inducing epithelial–mesenchymal transition and suppressing apoptosis through AKT pathway
Author(s) -
Xu Bing,
Zhou Minjie,
Qiu Wencai,
Ye Jueming,
Feng Qiming
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1039
Subject(s) - epithelial–mesenchymal transition , protein kinase b , cell migration , cancer research , gene knockdown , vimentin , small interfering rna , breast cancer , metastasis , pi3k/akt/mtor pathway , cell growth , downregulation and upregulation , chemistry , chemokine receptor , apoptosis , biology , cell , signal transduction , cancer , microbiology and biotechnology , chemokine , medicine , immunology , cell culture , transfection , inflammation , immunohistochemistry , genetics , biochemistry , gene
Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR 7 might induce the invasion, migration, and epithelial–mesenchymal transition ( EMT ) process of breast cancer. In this research, human breast cancer MCF ‐7 and MDA ‐ MB ‐231cells were treated with CCL 19 and small‐interfering RNA ( CCR 7 si RNA ) for activation and inhibition of CCR 7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR 7 on invasion and migration. The results demonstrated that CCL 19 mediated cell invasion and migration by inducing the EMT , with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR 7 revealed the changes compared with CCL 19 group and the control group. Knockdown of CCR 7 inhibits CCL 19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT . Moreover, we demonstrated that CCL 19‐induced AKT phosphorylation; however, CCR 7 si RNA suppressed CCL 19‐induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL 19/ CCR 7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR 7 may regard as a therapeutic target for the breast cancer treatment.