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The emerging role of class-3 semaphorins and their neuropilin receptors in oncology

Authors Nasarre P, Gemmill R, Drabkin H

Received 6 May 2014

Accepted for publication 24 July 2014

Published 24 September 2014 Volume 2014:7 Pages 1663—1687

DOI https://doi.org/10.2147/OTT.S37744

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Patrick Nasarre, Robert M Gemmill, Harry A Drabkin

Division of Hematology-Oncology, The Hollings Cancer Center and Medical University of South Carolina, Charleston, SC, USA


Abstract: The semaphorins, discovered over 20 years ago, are a large family of secreted or transmembrane and glycophosphatidylinositol-anchored proteins initially identified as axon guidance molecules crucial for the development of the nervous system. It has now been established that they also play important roles in organ development and function, especially involving the immune, respiratory, and cardiovascular systems, and in pathological disorders, including cancer. During tumor progression, semaphorins can have both pro- and anti-tumor functions, and this has created complexities in our understanding of these systems. Semaphorins may affect tumor growth and metastases by directly targeting tumor cells, as well as indirectly by interacting with and influencing cells from the micro-environment and vasculature. Mechanistically, semaphorins, through binding to their receptors, neuropilins and plexins, affect pathways involved in cell adhesion, migration, invasion, proliferation, and survival. Importantly, neuropilins also act as co-receptors for several growth factors and enhance their signaling activities, while class 3 semaphorins may interfere with this. In this review, we focus on the secreted class 3 semaphorins and their neuropilin co-receptors in cancer, including aspects of their signaling that may be clinically relevant.

Keywords: semaphorin, neuropilin, plexin

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