title: A cadherin switch underlies malignancy in high-grade gliomas.
abstract: Although the infiltrative behavior of malignant gliomas is one of their most critical aspects, the mechanisms underlying it have not yet been elucidated. To migrate in the brain parenchyma, malignant glioma cells need to bypass the cell-cell contact inhibitory signals. Here we propose that the blinding of cell-cell contact sensing in gliomas is caused by an unusual mechanism of cadherin switch, involving the replacement of N-cadherin with R-cadherin (Rcad) at the cell-cell junctions and the activation of ERK and p27. In our model of malignant glioma, we found that Rcad expression is necessary and sufficient to release cells from contact inhibition of proliferation, and is necessary, although not sufficient, for overriding contact inhibition of migration and for tumorigenicity. Altogether, these observations suggest that Rcad is a potential target for malignant glioma therapies.
authors.affiliation: U.O. Trasferimento Genico, IRCCS-AOU San Martino-IST, Largo Rosanna Benzi 10, Genoa, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Appolloni
authors.affiliation: U.O. Trasferimento Genico, IRCCS-AOU San Martino-IST, Largo Rosanna Benzi 10, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Barilari
authors.affiliation: Department of Experimental Medicine (DiMES), University of Genoa, Leon Battista Alberti 2, Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Caviglia
authors.affiliation: Department of Experimental Medicine (DiMES), University of Genoa, Leon Battista Alberti 2, Genoa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Gambini
authors.affiliation: U.O. Trasferimento Genico, IRCCS-AOU San Martino-IST, Largo Rosanna Benzi 10, Genoa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Reisoli
authors.affiliation: 1] U.O. Trasferimento Genico, IRCCS-AOU San Martino-IST, Largo Rosanna Benzi 10, Genoa, Italy [2] Department of Experimental Medicine (DiMES), University of Genoa, Leon Battista Alberti 2, Genoa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Malatesta
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D051379:Mice; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D015820:Cadherins; C489083:Cdh2 protein, mouse; D020574:Proto-Oncogene Proteins c-sis; C083970:R-cadherin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases