title: Ang II-AT1R increases cell migration through PI3K/AKT and NF-κB pathways in breast cancer.
abstract: Angiotensin II (Ang II), a biologically active peptide of the renin-angiotensin system (RAS), plays an important role in promoting cell migration via Angiotensin II type 1 receptor (AT1R). In this study, we examined the mechanisms by which Ang II affected cell migration in AT1R-positive MDA-MB-231 human breast cancer cells. Ang II increased cell migration and expression of matrix metalloproteinase (MMP)-2,-9 in a dose-dependent manner. Ang II-mediated cell migration was reduced by specific blocking of MMP-2 and MMP-9, as well as with pretreatment with inhibitors of AT1R, phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB. Similarly, Ang II-mediated expression of MMP-2,-9 was downregulated by pretreatment with inhibitors of AT1R and PI3K. In addition, Ang II treatment significantly induced phosphorylation of PI3K, Akt, and resulted in increased NF-κB activity. These findings suggest that Ang II activates the AT1R/PI3K/Akt pathway, which further activates IKKα/β and NF-κB, resulting in enhanced expression of MMP-2,-9 and migration in human breast cancer cells. Therefore, targeting Ang II/AT1R/PI3K/Akt/NF-κB signaling could be a novel anti-metastatic therapy for breast cancer.
authors.affiliation: Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hongbin
authors.initials: H
authors.lastname: Wang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Li
authors.forename: Mengru
authors.initials: M
authors.lastname: Cao
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Meng
authors.forename: Hui
authors.initials: H
authors.lastname: Pang
authors.forename: Hailin
authors.initials: H
authors.lastname: Li
authors.forename: Christina
authors.initials: C
authors.lastname: Nadolny
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Cai
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9