Department of Radiation Oncology, Lianyungang First People's Hospital, No.182, Tongguan Road, Lianyungang City, 222002, Jiangsu Province, China.
Target Oncol. 2016 Aug;11(4):501-5. doi: 10.1007/s11523-016-0422-0.
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.
最近的研究表明，神经纤毛蛋白-1（NRP-1）主要通过 VEGF 及其受体促进血管生成。它通过形成 NRP-1/VEGF（血管内皮生长因子）/VEGFR2（血管内皮生长因子受体 2）复合物促进肿瘤发生。除了 VEGF 及其受体，NRP-1 还与其他生长因子如血小板衍生生长因子（PDGF）和血小板衍生生长因子受体（PDGFR）结合。PDGF 在细胞增殖中起重要作用，特别是在血管形成中。此外，最近的研究表明，NRP-1 通过 NRP-1-ABL 途径促进血管生成，但不依赖于 VEGF-VEGFR2。RAD51 是参与 NRP1-ABL 和 PDGF（R）信号通路的一种蛋白质，其表达与细胞放射抗性和化学抗性呈正相关。NRP-1 激活 ABL 和 PDGF（R）的信号通路，上调 RAD51，从而诱导癌细胞对放疗和化疗产生抗性。此外，NRP-1 通过与纤维连接蛋白结合并激活 ABL 来激活肿瘤微环境，从而促进肿瘤生长。抑制 NRP-1 可能克服单独抑制 VEGF-VEGFR2 通路在癌症治疗中的局限性，并为癌症治疗提供新的思路。因此，我们综述了 NRP-1 在 VEGF-VEGFR2 非依赖性肿瘤发生中的作用。
