title: CCR7 mediates human breast cancer cell invasion, migration by inducing epithelial-mesenchymal transition and suppressing apoptosis through AKT pathway.
abstract: Chemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 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 CCL19 and small-interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 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 CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19-induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19-induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19-induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 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 CCR7 may regard as a therapeutic target for the breast cancer treatment.
authors.affiliation: Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Jueming
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Qiming
authors.identifier: http://orcid.org/0000-0002-7834-7376
authors.initials: Q
authors.lastname: Feng
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054400:Receptors, CCR7; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; CCR7; breast cancer; epithelial-mesenchymal transition; invasion