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  • Original Paper
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Interplay between scatter factor receptors and B plexins controls invasive growth

Oncogene volume 23, pages 5131–5137 (2004)Cite this article

Abstract

Met and Ron tyrosine kinases are members of the Scatter Factor Receptor family. Met is the receptor for hepatocyte growth factor while Ron is that for macrophage stimulating protein. On ligand stimulation, activation of these receptors induces ‘invasive growth’, a complex biological response involved in tissue morphogenesis and, when deregulated, in tumor progression and metastasis. Scatter Factor Receptors share structural homology with Plexins, transmembrane receptors for Semaphorins, a family of ligands originally identified as axon guidance molecules. A physical and functional association between Met and Plexin B1, the prototype of class B Plexin subfamily, has been previously demonstrated. Here, we show that both Met and Ron receptors can interact with each of the three members of class B Plexins, even in the absence of their ligands and that Plexin B1 ligand, Sema 4D, can induce activation of Met and Ron receptors, promoting an invasive response. Furthermore, in some human neoplastic cell lines Plexin B1 is overexpressed, constitutively tyrosine phosphorylated, and associated with Scatter Factor Receptors. These data extend the crosstalk previously described between Met and Plexin B1 to the entire families of Scatter Factor Receptors and class B Plexins and show that interaction with multiple upstream activators can finely tune the invasive growth process both in physiological conditions and in tumor growth and metastatization.

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Acknowledgements

We are grateful to L Tamagnone for Plexin B2 and B3 cDNAs and for the Sema 4D-AP construct; to A Follenzi for NIH-3T3 Ron cells; to M Tessier-Lavigne for DCC cDNA. We are deeply indebted to S Artigiani, L Tamagnone and our colleagues for constant discussions, with Antonella Cignetto for secretarial help and with Elaine Wright for editing the manuscript. The excellent technical assistance of L Palmas and R Albano is gratefully acknowledged.

This work was partly supported by Italian Association for Cancer Research to SG and PMC and by MURST COFIN to SG.

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  1. Paolo Conrotto and Simona Corso: Equally contributed to the work

Authors and Affiliations

  1. Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Candiolo, Torino, I-10060, Italy

    Paolo Conrotto, Simona Corso, Sara Gamberini, Paolo Maria Comoglio & Silvia Giordano

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  1. Paolo Conrotto
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  2. Simona Corso
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  4. Paolo Maria Comoglio
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  5. Silvia Giordano
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Correspondence to Silvia Giordano.

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Conrotto, P., Corso, S., Gamberini, S. et al. Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene 23, 5131–5137 (2004). https://doi.org/10.1038/sj.onc.1207650

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