Downregulation of ACE2/Ang-(1–7)/Mas axis promotes breast cancer metastasis by enhancing store-operated calcium entry

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

“…As previously mentioned, the components of the ACE2/Ang-(1–7)/MasR axis have various functions in different cancer types, and Yu et al suggested that the down-regulation of the ACE2/Ang-(1–7)/MasR axis could promote the metastasis of breast cancer (Yu et al, 2016). Zhou et al reported that the loss of ACE2 expression promotes the development of gallbladder cancer (Zong et al, 2015).…”

“…Reports have revealed that ACE2 may have both positive and negative roles in cancer therapies, and it has been identified as an inhibitor of cancer cell growth, metastasis, and angiogenesis in lung cancer (Feng et al, 2010), breast cancer (Yu et al, 2016), colon cancer (Bernardi et al, 2012), and pancreatic cancer (Zhou et al, 2011). Ang-(1–7) has been found to inhibit lung cancer cell growth (Gallagher and Tallant, 2004), but it promotes the migration and invasion of human renal cell carcinoma cells via the Mas-mediated AKT signaling pathway (Zheng et al, 2015), whereas the MasR has been demonstrated to act as an anti-tumor agent in breast cancer (Luo et al, 2015).…”

“…The ACE2/Ang-(1–7)/MasR axis, which represents a newly discovered component of the RAS, has been shown to be up-regulated or down-regulated in different cancers. Yu et al (2016) suggested that ACE2 expression is decreased in breast cancer, NSCLC (Feng et al, 2010), hepatocellular carcinoma (Ye et al, 2015), and pancreatic cancer (Zhou et al, 2009), and Zong et al (2015) reported that ACE2 levels are lower in gallbladder cancer cells than in normal gallbladder cells. Ang-(1–7) is generated primarily from Ang I or AngII via enzymatic cleavage; in recent studies, ACE2 has been identified as the main enzyme that generates Ang-(1–7), whereas ACE has been shown to be responsible for cleaving Ang-(1–7) to produce Ang-(1–5).…”

“…Moreover, researchers have suggested that decreased ACE2 activity may reflect the presence of cancer associated with diabetes (Pedersen et al, 2015). Yu et al (2016) reported low ACE2 expression levels in breast cancer samples with distant metastasis and in samples of tumors that had spread to lymph nodes. Ye et al reported that patients with higher levels of ACE2 expression had longer survival times than those with a lower levels of ACE2 expression, which suggests that a low level of ACE2 expression may be a useful indicator of poor prognoses for patients with hepatocellular carcinoma (Ye et al, 2015).…”

“…Yu et al (2016) reported that the RAS is an important component of the tumor microenvironment and plays a key role in promoting cancer cell proliferation, metabolism, migration, and invasion, as well as angiogenesis. These authors observed that the branch of the ACE2/Ang-(1–7)/MasR axis connected to the RAS is associated with anti-proliferative and anti-metastatic properties, and they further found that the ACE2 protein levels are negatively correlated with the metastatic ability of breast cancer cells and the grade of breast tumors and showed that the up-regulation of the ACE2/Ang-(1–7)/MasR axis could inhibit breast cancer cell metastasis in vivo and in vitro (Yu et al, 2016).…”