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Multifaceted Role of Neuropilins in Cancer

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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.

Keywords: Angiogenesis; Nrp1; Nrp2; cancer; metastasis; neuropilins; plexins; semaphorins; signaling; targeted therapy

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986711796642544

Publication date: August 1, 2011

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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