Multifaceted Role of Neuropilins in Cancer

Abstract

Neuropilins comprise two homologous widely-expressed single-pass plasma membrane receptors (Nrp1 and Nrp2), originally identified for binding secreted Semaphorins and Vascular Endothelial Growth Factors (in association with Plexins and VEGF-Receptors). Semaphorins have been implicated with opposite functions in cancer: either as putative tumor suppressors and anti-angiogenic factors, or mediating tumour angiogenesis, invasion and metastasis. Moreover, due to their implication in VEGF signaling, neuropilins regulate vascular development and tumor angiogenesis. Recent evidence further suggests a role of neuropilins in cancer progression due to their interaction with receptor tyrosine kinases, adhesion molecules, and integrins. Furthermore, neuropilins have been implicated in response to additional growth factors, such as Hepatocyte Growth Factor, Fibroblast Growth Factor, Transforming Growth Factor beta, Galectin, etc. Altogether, these data seem to qualify neuropilins as signaling platforms on the cell surface, potentially capable of regulating cancer cells, as well as cells of the tumor microenvironment. Intriguingly, clinical-pathological data often indicate a correlation between increased expression of neuropilins and advanced stage tumors with poor prognosis. In this article, we will review the current experimental evidence about the functional role of neuropilins in cancer and the underlying molecular mechanisms.

Antiangiogenic agent sunitinib induces epithelial to mesenchymal transition and accelerates motility of colorectal cancer cells

“…The sunitinib-conditioned cells did not increase all of VEGF-R tested (Fig. 3A-C), suggesting that the cells do not utilize VEGF -Rs under the VEGF-R inhibited conditions, and that they may switch the VEGF-R-related receptors that can bind VEGF and transduce its signal, such as NRP1 and NRP2 (16). To test this possibility, we determined expression levels of NRP1 and NRP2 were measured using RT-qPCR.…”

“…It seems to be reasonable, since NRP1 is a receptor for VEGF but is not the target of sunitinib (16). There is increasing evidence that NRP1 plays critical roles in the evasive phenotype of several cancer cells.…”

Le trafic membranaire, un nouvel acteur du guidage axonal

“…Les applications thérapeutiques potentielles sont d'une grande portée puisque les molécules de guidage sont aussi impliquées dans le développement de maladies neurodégénératives, de lésions nerveuses et de cancers [9,10]. L'utilisation des neurotoxines clostridiales pourrait être envisagée pour stimuler la régénération neuronale après une lésion nerveuse (en retirant la sensibilité aux molécules répulsives), pour Syb2, les axones frontaux du corps calleux sont désorganisés et défasci-culés comme dans le modèle d'invalidation de Séma3A, ces effets n'étant pas retrouvés après l'invalidation de Séma3C.…”

Semaphorin Signaling in Cardiovascular Development

“…However, this is generally not the case with (class 3) semaphorins, with the exception of semaphorin 3e (Sema3e), which require an initial interaction with a neuropilin co-receptor (Nrp1/Nrp2) to transduce their signal to plexin receptors (Gu et al, 2003). Neuropilins are promiscuous co-receptors regarding both ligands and receptor partners that participate in a broad range of signaling pathways (Gu et al, 2003;Hillman et al, 2011;Muders, 2011;Neufeld et al, 2002;Rizzolio and Tamagnone, 2011). Importantly with regard to the cardiovascular system, neuropilins can partner with the vascular endothelial growth factor (Vegf) receptor to mediate angiogenic Vegf signaling to endothelial cells.…”