Fig. 3

Schematic diagram of the roles of (P) RR in pathways that contribute to oncogenesis, as well as cancer progression and metastasis. In the Wnt/β-catenin pathway, (P) RR is an important component of the Wnt receptor complex and acts as an adaptor between LRP6 and V-ATPase, thus facilitates the binding of Wnt ligands (Wnts) to the Wnt receptor complex, internalization of the complex as a signalosome and Wnt signaling transduction. Full-length (P) RR or M8–9 fragment also interacts with the V-ATPase, on both plasma and vesicle membranes, thus assists it to generate a proton gradient across the plasma membrane that is crucial for LRP6 phosphorylation and subsequent β-catenin activation, as well as to acidize of the vesicles. On binding with the prorenin/renin, (P) RR further contributes to signal transduction of the PI3K/AKT/mTOR and MAPK/ERK pathways, directly or through the induction of reactive oxygen species (ROS) formation. The binding of prorenin or renin to (P) RR enhances their enzymatic activity, which further facilitates the catalysis of angiotensinogen (AGT) to angiotensin (Ang) I. Then, Ang I will be acted on by angiotensin-converting enzyme (ACE) to produce Ang II, which triggers Ang II receptor-mediated signal transduction, leading to elevated tissue RAS activity as well as the formation of NF-κB and transforming growth factor (TGF)β