Abstract
Exploiting pleiotropic activities of semaphorins as multi‐target therapies for cancer
Highlights
Sema3E is one of the SEMAs implicated in tumour invasion and metastatization and its expression correlates with the metastatic process
Casazza et al demonstrate that Uncl-Sema3E interferes with the endogenous Sema3E signalling, but is unable to induce the association of PlxnD1 with ErbB2 in the tumour cell context
In tumour cells, binding of p61-Sema3E to PlxnD1 promotes the formation of a heteromultimeric complex with ErbB2 receptor tyrosine kinases (RTKs) that leads to its transactivation and further activation of ErbB2-EGFR-mediated pro-invasive and pro-metastatic signalling pathway
Summary
Sema3E is one of the SEMAs implicated in tumour invasion and metastatization and its expression correlates with the metastatic process. Sema3E exerts pleiotropic activities through its specific receptor, Plexin-D1 (PlxnD1), including a collapsing pro-apoptotic response in endothelial cells and a pro-invasive and prometastatic effect on tumour cells. On the contrary, ErbB2 plays a master role in the pro-invasive, pro-metastatic properties of p61-Sema3E with PlxnD1 forming a complex with ErbB2 that results in its transactivation and further activation of EGFR-ErbB2mediated signalling pathways (Casazza et al, 2010; Fig 1A).
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