Figure 2.

A schema showing the effect of the renin–angiotensin system (RAS) and its convergent signaling pathways on the tumor microenvironment to influence cellular proliferation, invasiveness, and cell survival in cancer development. The RAS interacts with downstream pathways, such as the Ras/RAF/MEK/ERK (light blue) pathway and the PI3K/AKT/mTOR (dark blue) pathway, and the upstream Wnt/β-catenin pathway (intermediate blue) that influence cellular proliferation, migration, inhibition of apoptosis, migration, and invasion (see text). PRR, pro-renin receptor; LRP6, low-density lipoprotein receptor-related protein; Fzd, frizzled receptor; Cath G, cathepsin G; Cath B, cathepsin B; Cath D, cathepsin D; ACE1, angiotensin-converting enzyme 1; ACE2, angiotensin-converting enzyme 2; ADP, adenosine diphosphate; AGT, angiotensinogen; ATP, adenosine triphosphate; Ang(1–7), angiotensin (1–7); Ang(1–9), angiotensin (1–9); AP-A, aminopeptidase-A; NEP, neutral endopeptidase; AP-N, aminopeptidase-N; ATI, angiotensin I; ATII, angiotensin II; ATIII, angiotensin III; ATIV, angiotensin IV; AT₁R, angiotensin II receptor 1; AT₂R, angiotensin II receptor 2; AT₄R, angiotensin II receptor 4; MrgD, Mas-related-G protein coupled receptor; MasR, Mas receptor; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa B; TGF-β₁, transforming growth factor-β₁; V-ATPase, vacuolar H⁺-adenosine triphosphate.