Interplay between scatter factor receptors and B plexins controls invasive growth.
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.
Conrotto
Paolo
P
Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, I-10060 Candiolo, Torino, Italy.
Corso
Simona
S
Gamberini
Sara
S
Comoglio
Paolo Maria
PM
Giordano
Silvia
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003094:Collagen; D004338:Drug Combinations; D006801:Humans; D007797:Laminin; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010766:Phosphorylation; D011509:Proteoglycans; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; C093224:CD100 antigen; D004338:Drug Combinations; D007797:Laminin; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D039961:Semaphorins; C059485:matrigel; D014443:Tyrosine; D003094:Collagen; D019859:Proto-Oncogene Proteins c-met; D000469:Alkaline Phosphatase