NRP1

Case study 1: Liang Jin, 2024

Neuropilin-1 (NRP1), a transmembrane glycoprotein, plays an important role in the malignant progression of gliomas; however, its role in chemoresistance is not fully understood. In this study, the researchers observed the effects of NRP1 on the stemness and chemoresistance of glioma cells and the mediating role of Yes-associated protein (YAP). They constructed NRP1 overexpressing LN-229 glioma cells. Cells were treated with recombinant NRP1 protein (rNRP1) and the YAP inhibitor Super-TDU when necessary. MTT assay was used to detect the sensitivity of cells to temozolomide (TMZ). Western blotting was performed to detect cellular CD133, CD44, p-LATS1, and p-YAP protein expression. Immunofluorescence and flow cytometry were used to detect the subcellular localization of YAP and apoptosis, respectively.

The results showed that NRP1 overexpression and rNRP1 treatment enhanced self-renewal, TMZ resistance, and CD133 and CD44 protein expression in LN-229 cells. NRP1 overexpression and rNRP1 treatment also induced LATS1 and YAP dephosphorylation and YAP nuclear translocation. Super-TDU inhibits NRP1 overexpression-induced enhanced self-renewal and TMZ resistance in LN-229 cells.

Fig1. LN-229 cells were transfected with rNRP1 treatment for 24 h, and the number and diameter of cell spheres were measured after 7 d of incubation using stem cell sphere culture medium.

Fig2. LN-229 cells were treated with rNRP1 (75, 150, 300 ng/mL) for 24 h. Western blotting detected CD133 and CD44 protein expression.

Case study 2: Peng Zhang, 2023

Prostate cancer (PCa) is the most common malignant tumor with a high global incidence in males. The mechanism underlying PCa progression is still not clear. This study observed that NRP1 was highly expressed in PCa and associated with poor prognosis in PCa patients. Functionally, NRP1 depletion attenuated the proliferation and migration ability of PCa cells in vitro and in vivo, while NRP1 overexpression promoted PCa cell proliferation and migration. Moreover, it was observed that NRP1 depletion induced G1 phase arrest in PCa cells. Mechanistically, HIF1α is bound to the specific promoter region of NRP1, thereby regulating its transcriptional activation. Subsequently, NRP1 interacted with EGFR, leading to EGFR phosphorylation. This study also provided evidence that the b1/b2 domain of NRP1 was responsible for the interaction with the extracellular domain of EGFR. Moreover, EGFR mediated NRP1-induced activation of the AKT signaling pathway, which promoted the malignant progression of PCa. In addition, the administration of NRP1 inhibitor EG01377 significantly inactivated the EGFR/AKT signaling axis, thereby suppressing PCa progression.

Fig3. Immunoblot assay elucidates that ectopic overexpression of NRP1 promotes EGFR phosphorylation level.

Fig4. Identification of the b1/b2 domain of NRP1 mediating its interaction with EGFR.

Fig1. NRP1 regulates multiple signalling pathways in endothelial cells. (Claudio Raimondi, 2016)

Fig2. VEGF165 induces complex formation between NRP1 and VEGFR2 to enhance VEGFR2 signaling in endothelial cells in vitro. (Alice Plein, 2014)

NRP1 involved in several pathways and played different roles in them. We selected most pathways NRP1 participated on our site, such as Axon guidance, HTLV-I infection, which may be useful for your reference. Also, other proteins which involved in the same pathway with NRP1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

NRP1 has several biochemical functions, for example, coreceptor activity, cytokine binding, growth factor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by NRP1 itself. We selected most functions NRP1 had, and list some proteins which have the same functions with NRP1. You can find most of the proteins on our site.

NRP1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with NRP1 here. Most of them are supplied by our site. Hope this information will be useful for your research of NRP1.

VEGFA; KDR; FLNA; FLT1; RPL27; ptsN1; CSNK2A2