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Role of NRP-1 in VEGF-VEGFR2-Independent Tumorigenesis

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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.

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Acknowledgments

This was supported by the National Natural Science Foundation of China (grant no. 81472792) and the National Natural Science Foundation of Jiangsu Province (BK20151279).

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Correspondence to Xiaodong Jiang.

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Chenxi Hu and Xiaodong Jiang have no interest to declare.

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Hu, C., Jiang, X. Role of NRP-1 in VEGF-VEGFR2-Independent Tumorigenesis. Targ Oncol 11, 501–505 (2016). https://doi.org/10.1007/s11523-016-0422-0

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