Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells
Tocci, Johanna M.
Del Valle Suberbordes, Melisa
Kordon, Edith C.
Angiotensin (Ang) II, the main effector peptide of the renin-angiotensin system, has been implicated in multiple aspects of cancer progression such as proliferation, migration, invasion, angiogenesis and metastasis. Ang-(1-7), is a biologically active heptapeptide, generated predominantly from AngII by the enzymatic activity of angiotensin converting enzyme 2. Previous studies have shown that Ang-(1-7) counterbalances AngII actions in different pathophysiological settings. In this study, we have analysed the impact of Ang( 1-7) on AngII-induced pro-tumorigenic features on normal murine mammary epithelial cells NMuMG and breast cancer cells MDA-MB-231. AngII stimulated the activation of the survival factor AKT in NMuMG cells mainly through the AT1 receptor. This PI3K/AKT pathway activation also promoted epithelial-mesenchymal transition (EMT). Concomitant treatment of NMuMG cells with AngII and Ang-(1-7) completely abolished EMT features induced by AngII. Furthermore, Ang-(1-7) abrogated AngII induced migration and invasion of the MDA-MB-231 cells as well as pro-angiogenic events such as the stimulation of MMP-9 activity and VEGF expression. Together, these results demonstrate for the first time that Ang-(1-7) counteracts tumor aggressive signals stimulated by AngII in breast cancer cells emerging the peptide as a potential therapy to prevent breast cancer progression.
AKT , Angiotensin ii , Angiotensin-(1-7) , Breast cancer cells , Epithelial-mesenchymal transition
Cambados, N., Walther, T., Nahmod, K., Tocci, J. M., Rubinstein, N., Böhme, I., Simian, M., Sampayo, R., Suberbordes, M. D. V. and Kordon, E. C. (2017) 'Angiotensin-(1-7) counteracts the transforming effects triggered by angiotensin II in breast cancer cells', Oncotarget, 8(51), pp. 88475-88487. doi: 10.18632/oncotarget.19290