The ACE2/Angiotensin-(1–7)/Mas Receptor Axis: Pleiotropic Roles in Cancer

Abstract

Cancer remains one of the most common causes of death and disability and represents a major economic burden in industrialized nations. The renin-angiotensin system (RAS) has been well-recognized as one of the most important regulators of both normal and pathological physiological processes in the brain, kidney, heart, and blood vessels. The activation of the angiotensin-converting enzyme 2/angiotensin-(1–7)/mitochondrial assembly receptor [ACE2/Ang-(1–7)/MasR] axis, which is one component of the RAS, has recently been identified as a critical component of pulmonary systems, gastric mucosa, and cancer. However, the ability of the ACE2/Ang-(1–7)/MasR axis to suppress or promote cancer has not been fully elucidated. In this review, we focus on recent experimental and clinical studies investigating the basic properties, roles, and mechanisms of ACE2, Ang-(1–7), and the MasR, as well as the axis pathway, to provide insights into possible therapeutic strategies for treating cancer that target the ACE2/Ang-(1–7)/MasR axis.

Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1‐7)/MAS receptor axes in human mesangial cells

“…) and, as with ACE2, both ANG (1‐7) and the MAS receptor exert contrasting effects depending on the tissue in question (Xu et al. ). Zimpelmann and Burns showed that MAS receptor antagonist decreases the growth stimulatory pathways induced by ANG (1‐7) in MCs, while AT1 and AT2 receptor antagonists were unable to reproduce these results (Zimpelmann and Burns ).…”

Natural and grafted cyclotides in cancer therapy: An insight

“…The renin‐angiotensin system (RAS) is well known as a regulator of blood pressure and homeostasis, but recently, angiotensin (1‐7) has been associated with antiproliferative and antiangiogenic properties. Angiotensin (1‐7) interacts with its unique receptor MAS1 in lung cancer cells, causing a decline in the cyclooxygenase 2 activity thereby inhibiting cell growth . However, the therapeutic potential of angiotensin (1‐7) was limited by the poor pharmacokinetics.…”

The potential actions of angiotensin‐converting enzyme II (ACE2) activator diminazene aceturate (DIZE) in various diseases

“…Several studies have linked the presence and more specifically the upregulation of AGTR1 (the gene that codes the AT1 R) to the pathogenesis of certain cancers, particularly invasive breast carcinoma . Studies have also linked ACE2 expression and its potential mechanism in numerous cancer cells and tissues by counter regulating ACE activity . It has been demonstrated in patients with breast cancer that elevated expression of ACE2 was associated with increased relapse‐free survival (RFS) .…”

“…The existing literature highlights the role of increased ACE2 expression in the reduction of cell migration, proliferation and metastasis, DIZE may be a possible target to reduce the side effects of cancer therapy. The pathway of DIZE in relation to the RAS in vascular function is well established and it is hypothesised that the same pathway is exhibited in cancer cells to reduce cancer metastasis …”

“…54,55 Studies have also linked ACE2 expression and its potential mechanism in numerous cancer cells and tissues by counter regulating ACE activity. 56 It has been demonstrated in patients with breast cancer that elevated expression of ACE2 was associated with increased relapse-free survival (RFS). 57 Elevated ACE2 expression was also associated with inhibition of cell migration and proliferation in human umbilical endothelial cells (HUVECS).…”