VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression
Menée in vitro, cette étude met en évidence une nouvelle fonction oncogène, indépendante du mécanisme d'angiogenèse, attribuée au facteur de croissance de l'endothélium vasculaire
Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF or VEGF-A) is a pivotal driver of cancer angiogenesis that is a central therapeutic target in treatment of malignancy. However, little work has been devoted to investigating functions of VEGF that are independent of its pro-angiogenic activity. Here we report that VEGF produced by tumor cells acts in an autocrine manner to promote cell growth through interaction with the VEGF receptor neuropilin-1 (NRP-1). Reducing VEGF expression by tumor cells induced a differentiated phenotype in vitro and inhibited tumor-forming capacity in vivo independent of effects on angiogenesis. Autocrine activation of tumor cell growth was dependent on signaling through NRP-1 and Ras was determined to a critical effector signaling molecule downstream of NRP-1. Our findings define a novel function for VEGF in de-differentiation of tumor cells, expanding its role in cancer beyond its known pro-angiogenic function.