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Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice

Semaphorin 3E (Sema3E) is a secreted molecule implicated in axonal path finding and inhibition of developmental and postischemic angiogenesis. Sema3E is also highly expressed in metastatic cancer cells, but its mechanistic role in tumor progression was not understood. Here we show that expression of...

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Main Authors: Casazza, Andrea (Author) , Finisguerra, Veronica (Author) , Capparuccia, Lorena (Author) , Camperi, Andrea (Author) , Swiercz, Jakub M. (Author) , Rizzolio, Sabrina (Author) , Rolny, Charlotte (Author) , Christensen, Claus (Author) , Bertotti, Andrea (Author) , Sarotto, Ivana (Author) , Risio, Mauro (Author) , Trusolino, Livio (Author) , Weitz, Jürgen (Author) , Schneider, Martin (Author) , Mazzone, Massimiliano (Author) , Comoglio, Paolo M. (Author) , Tamagnone, Luca (Author)
Format: Article (Journal)
Language:English
Published: July 26, 2010
In: The journal of clinical investigation
Year: 2010, Volume: 120, Issue: 8, Pages: 2684-2698
ISSN:1558-8238
DOI:10.1172/JCI42118
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1172/JCI42118
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Author Notes:Andrea Casazza, Veronica Finisguerra, Lorena Capparuccia, Andrea Camperi, Jakub M. Swiercz, Sabrina Rizzolio, Charlotte Rolny, Claus Christensen, Andrea Bertotti, Ivana Sarotto, Mauro Risio, Livio Trusolino, Jurgen Weitz, Martin Schneider, Massimiliano Mazzone, Paolo M. Comoglio, and Luca Tamagnone
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Summary:Semaphorin 3E (Sema3E) is a secreted molecule implicated in axonal path finding and inhibition of developmental and postischemic angiogenesis. Sema3E is also highly expressed in metastatic cancer cells, but its mechanistic role in tumor progression was not understood. Here we show that expression of Sema3E and its receptor Plexin D1 correlates with the metastatic progression of human tumors. Consistent with the clinical data, knocking down endogenous expression of either Sema3E or Plexin D1 in human metastatic carcinoma cells hampered their metastatic potential when injected into mice, while tumor growth was not markedly affected. Conversely, overexpression of exogenous Sema3E in cancer cells increased their invasiveness, transendothelial migration, and metastatic spreading, although it inhibited tumor vessel formation, resulting in reduced tumor growth in mice. The proinvasive and metastatic activity of Sema3E in tumor cells was dependent on transactivation of the Plexin D1-associated ErbB2/Neu oncogenic kinase. In sum, Sema3E-Plexin D1 signaling in cancer cells is crucially implicated in their metastatic behavior and may therefore be a promising target for strategies aimed at blocking tumor metastasis.
Item Description:Gesehen am 26.01.2023
Physical Description:Online Resource
ISSN:1558-8238
DOI:10.1172/JCI42118

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