Cytoplasmic neuropilin 2 is associated with metastasis and a poor prognosis in early tongue cancer patients

Ong, Hui Shan; Gokavarapu, Sandhya; Xu, Qin; Tian, Zhen; Li, J.; Ji, Tong; Zhang, C.P.

doi:10.1016/j.ijom.2017.03.035

Cited by 14 publications

(6 citation statements)

References 23 publications

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“…Thus, NRP2 may regulate SSH1 transcription to increase its expression. A previous study showed that NRP2, a transmembrane protein, can dissociate from the membrane to the cytoplasm in tongue cancer and colon cancer cells [ 32 , 33 ]. In eukaryotic cells, macromolecules such as proteins and RNA in the cytoplasm are separated from the translational machinery in the nucleus by nuclear pore complexes [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Vascular NRP2 triggers PNET angiogenesis by activating the SSH1-cofilin axis

Luo

et al. 2020

Cell Biosci

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Background Angiogenesis is a critical step in the growth of pancreatic neuroendocrine tumors (PNETs) and may be a selective target for PNET therapy. However, PNETs are robustly resistant to current anti-angiogenic therapies that primarily target the VEGFR pathway. Thus, the mechanism of PNET angiogenesis urgently needs to be clarified. Methods Dataset analysis was used to identify angiogenesis-related genes in PNETs. Immunohistochemistry was performed to determine the relationship among Neuropilin 2 (NRP2), VEGFR2 and CD31. Cell proliferation, wound-healing and tube formation assays were performed to clarify the function of NRP2 in angiogenesis. The mechanism involved in NRP2-induced angiogenesis was detected by constructing plasmids with mutant variants and performing Western blot, and immunofluorescence assays. A mouse model was used to evaluate the effect of the NRP2 antibody in vivo, and clinical data were collected from patient records to verify the association between NRP2 and patient prognosis. Results NRP2, a VEGFR2 co-receptor, was positively correlated with vascularity but not with VEGFR2 in PNET tissues. NRP2 promoted the migration of human umbilical vein endothelial cells (HUVECs) cultured in the presence of conditioned medium PNET cells via a VEGF/VEGFR2-independent pathway. Moreover, NRP2 induced F-actin polymerization by activating the actin-binding protein cofilin. Cofilin phosphatase slingshot-1 (SSH1) was highly expressed in NRP2-activating cofilin, and silencing SSH1 ameliorated NRP2-activated HUVEC migration and F-actin polymerization. Furthermore, blocking NRP2 in vivo suppressed PNET angiogenesis and tumor growth. Finally, elevated NRP2 expression was associated with poor prognosis in PNET patients. Conclusion Vascular NRP2 promotes PNET angiogenesis by activating the SSH1/cofilin/actin axis. Our findings demonstrate that NRP2 is an important regulator of angiogenesis and a potential therapeutic target of anti-angiogenesis therapy for PNET.

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Section: Discussionmentioning

confidence: 99%

Vascular NRP2 triggers PNET angiogenesis by activating the SSH1-cofilin axis

Luo

et al. 2020

Cell Biosci

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“…Neuropilins (NRPs), transmembrane non-tyrosine-kinase glycoproteins, are the receptors of class-3 semaphorins, including two highly conserved homologous members, neuropilin-1 (NRP1) and neuropilin-2 (NRP2) (5). A great deal of researches shows that NRP2 is upregulated and associated with unfavorable prognosis in a variety of tumors (6,7). As multifunctional membrane proteins, NRP2 enhances or modifies signal transduction pathways through interactions with various receptors or ligands to modulate cancer progression (8).…”

Section: Introductionmentioning

confidence: 99%

N2E4, a Monoclonal Antibody Targeting Neuropilin-2, Inhibits Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma via Suppressing FAK/Erk/HIF-1α Signaling

Wang

et al. 2021

Front. Oncol.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with extremely limited treatment; the effective targeting strategy stays an urgent unmet need. Neuropilin-2 (NRP2), a multifunctional transmembrane non-tyrosine-kinase glycoprotein, enhances various signal transduction pathways to modulate cancer progression. However, the application value of NRP2 as a therapeutic target in pancreatic cancer is still unclear. Here, we detected the elevated NRP2 was associated with the poor prognosis of pancreas carcinoma. The mouse monoclonal antibody targeting NRP2 (N2E4) that could specifically bind to PDAC cells was developed. Moreover, N2E4 inhibits PDAC proliferation, migration, and invasion in vitro, and repressed growth and metastasis in vivo. Mechanistically, the effect of N2E4 was mainly related to the blocking of interaction between NRP2 with integrinβ1 to inhibit FAK/Erk/HIF-1a/VEGF signaling. Therefore, N2E4 has the potential for targeting therapy of PDAC. This study lays a foundation for the future development of NRP2-based targeted therapy for PDAC.

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“…NRPs have been associated with increased malignant potential and poor prognosis in various human cancers (19,22,(39)(40)(41). In addition to their potential as biomarkers, efforts are underway to develop NRP1 or NRP2 as therapeutic targets (42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability and Motility

et al. 2021

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The neuropilins NRP1 and NRP2 are multifunctional glycoproteins that have been implicated in several cancer-related processes including cell survival, migration, and invasion in various tumor types. Here, we examine the role of neuropilins in hepatoblastoma (HB), the most common pediatric liver malignancy. Using a combination of immunohistochemistry, RNA analysis and western blotting, we observed high level expression of NRP1 and NRP2 in 19 of 20 HB specimens and in a majority of human HB cell lines (HUH6 and five cell lines established from patient-derived xenografts) studied but not in normal hepatocytes. Silencing of NRP2 expression in HUH6 and HB-282 HB cells resulted in decreased cell viability, impaired cytoskeleton remodeling, and reduced cell motility, suggesting that NRP2 contributes to the malignant phenotype. We propose that neuropilins warrant further investigation as biomarkers of HB and potential therapeutic targets.

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Cytoplasmic neuropilin 2 is associated with metastasis and a poor prognosis in early tongue cancer patients

Cited by 14 publications

References 23 publications

Vascular NRP2 triggers PNET angiogenesis by activating the SSH1-cofilin axis

Vascular NRP2 triggers PNET angiogenesis by activating the SSH1-cofilin axis

N2E4, a Monoclonal Antibody Targeting Neuropilin-2, Inhibits Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma via Suppressing FAK/Erk/HIF-1α Signaling

Neuropilin-2 Is Associated With Increased Hepatoblastoma Cell Viability and Motility

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