title: Role of NRP-1 in VEGF-VEGFR2-Independent Tumorigenesis.
abstract: Recent studies suggest that neuropilin-1 (NRP-1) promotes angiogenesis mainly via VEGF and its receptors. It promotes tumorigenesis via formation of the NRP-1/ VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) complex. In addition to VEGF and its receptors, NRP-1 also binds with other growth factors such as platelet-derived growth factor (PDGF) and platelet-derived growth factor receptor (PDGFR). PDGF plays important roles in cellular proliferation and, in particular, blood vessel formation. Moreover, recent studies show that NRP-1 promotes angiogenesis via the NRP-1-ABL pathway, but independent of VEGF-VEGFR2. RAD51 is a protein involved in the signaling pathways of NRP1-ABL and PDGF(R), the expression of which is positively associated with cell radioresistance and chemoresistance. NRP-1 activates the signaling pathways of ABL and PDGF(R) to upregulate RAD51, which induces resistance to radiotherapy and chemotherapy in cancer cells. Furthermore, NRP-1 activates the tumor microenvironment by binding with fibronectin and activating ABL, thereby promoting tumor growth. Inhibition of NRP-1 may overcome the limitations of individually inhibiting the VEGF-VEGFR2 pathway in cancer therapy and provide new ideas for cancer treatment. Therefore, we review the role of NRP-1 in VEGF-VEGFR2-independent tumorigenesis.
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No.182, Tongguan Road, Lianyungang City, 222002, Jiangsu Province, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Lianyungang First People's Hospital, No.182, Tongguan Road, Lianyungang City, 222002, Jiangsu Province, China. jxdysy1970@163.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiang
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation; D006801:Humans; D039942:Neuropilin-1 / Q000235:genetics*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1