Abstract
Identifying novel targets that control both tumorigenesis and angiogenesis can aid in developing a more potent anti-angiogenic therapeutic strategy. We previously reported that reduction of FRG1 is associated with increased p38-MAPK signaling in prostate cancer and with elevated MEK-ERK signaling in breast cancer. Here, we reveal the role of FRG1 in tumor angiogenesis. Our findings demonstrate that depleted FRG1 levels enhance the proliferation, migration, and tubule formation of HUVECs in a paracrine manner, and this was further substantiated in multiple animal models. Mechanistically, FRG1 depletion activated the expression of FGF2 in breast cancer cells, which triggered the ERK/AKT cascade in endothelial cells. As FRG1 affects multiple tumorigenic properties and it is upstream of FGF2, it can be explored as a therapeutic target that is less prone to resistance.