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dc.contributor.authorRaimondi, C
dc.contributor.authorCalleja, V
dc.contributor.authorFerro, R
dc.contributor.authorFantin, A
dc.contributor.authorRiley, AM
dc.contributor.authorPotter, BV
dc.contributor.authorBrennan, CH
dc.contributor.authorMaffucci, T
dc.contributor.authorLarijani, B
dc.contributor.authorFalasca, M
dc.date.accessioned2016-06-07T14:17:37Z
dc.date.issued2016-05-20
dc.date.issued2016
dc.date.issued2016-05-20
dc.date.submitted2016-06-04T08:55:17.478Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/12725
dc.description.abstractStrong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs.
dc.format.extent26142 - ?
dc.languageENG
dc.language.isoenen_US
dc.rightsCC-BY
dc.titleA Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion.
dc.typeJournal Article
dc.rights.holder© 2016, Rights Managed by Nature Publishing Group
dc.identifier.doi10.1038/srep26142
dc.relation.isPartOfSci Rep
dc.relation.isPartOfSci Rep
dc.relation.isPartOfSci Rep
pubs.author-urlhttp://www.ncbi.nlm.nih.gov/pubmed/27199173
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Cell Biology and Cutaneous Research
pubs.organisational-group/Queen Mary University of London/Faculty of Science & Engineering
pubs.organisational-group/Queen Mary University of London/Faculty of Science & Engineering/Biological and Chemical Sciences - Staff
pubs.publication-statusPublished online
pubs.volume6


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