Please use this identifier to cite or link to this item:
https://doi.org/10.1038/ncomms15866
DC Field | Value | |
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dc.title | Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein | |
dc.contributor.author | Laviolette L.A. | |
dc.contributor.author | Mermoud J. | |
dc.contributor.author | Calvo I.A. | |
dc.contributor.author | Olson N. | |
dc.contributor.author | Boukhali M. | |
dc.contributor.author | Steinlein O.K. | |
dc.contributor.author | Roider E. | |
dc.contributor.author | Sattler E.C. | |
dc.contributor.author | Huang D. | |
dc.contributor.author | Teh B.T. | |
dc.contributor.author | Motamedi M. | |
dc.contributor.author | Haas W. | |
dc.contributor.author | Iliopoulos O. | |
dc.date.accessioned | 2020-09-06T16:04:46Z | |
dc.date.available | 2020-09-06T16:04:46Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Laviolette L.A., Mermoud J., Calvo I.A., Olson N., Boukhali M., Steinlein O.K., Roider E., Sattler E.C., Huang D., Teh B.T., Motamedi M., Haas W., Iliopoulos O. (2017). Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein. Nature Communications 8 : 15866. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms15866 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/174490 | |
dc.description.abstract | Germline mutations in the Folliculin (FLCN) tumour suppressor gene result in fibrofolliculomas, lung cysts and renal cancers, but the precise mechanisms of tumour suppression by FLCN remain elusive. Here we identify Rab7A, a small GTPase important for endocytic trafficking, as a novel FLCN interacting protein and demonstrate that FLCN acts as a Rab7A GTPase-activating protein. FLCN-/- cells display slower trafficking of epidermal growth factor receptors (EGFR) from early to late endosomes and enhanced activation of EGFR signalling upon ligand stimulation. Reintroduction of wild-type FLCN, but not tumour-associated FLCN mutants, suppresses EGFR signalling in a Rab7A-dependent manner. EGFR signalling is elevated in FLCN-/- tumours and the EGFR inhibitor afatinib suppresses the growth of human FLCN-/- cells as tumour xenografts. The functional interaction between FLCN and Rab7A appears conserved across species. Our work highlights a mechanism explaining, at least in part, the tumour suppressor function of FLCN. © The Author(s) 2017. | |
dc.publisher | Nature Publishing Group | |
dc.source | Unpaywall 20200831 | |
dc.subject | afatinib | |
dc.subject | early endosome antigen 1 | |
dc.subject | epidermal growth factor receptor | |
dc.subject | estrone | |
dc.subject | guanosine triphosphatase activating protein | |
dc.subject | immunoglobulin G antibody | |
dc.subject | lysosome associated membrane protein 1 | |
dc.subject | protein kinase B | |
dc.subject | rab7a protein | |
dc.subject | scatter factor | |
dc.subject | scatter factor receptor | |
dc.subject | STAT3 protein | |
dc.subject | tumor suppressor protein | |
dc.subject | unclassified drug | |
dc.subject | EGFR protein, human | |
dc.subject | epidermal growth factor receptor | |
dc.subject | FLCN protein, human | |
dc.subject | oncoprotein | |
dc.subject | Rab protein | |
dc.subject | Rab7 protein | |
dc.subject | tumor suppressor protein | |
dc.subject | anatomy | |
dc.subject | cancer | |
dc.subject | cells and cell components | |
dc.subject | enzyme | |
dc.subject | enzyme activity | |
dc.subject | gene | |
dc.subject | gene expression | |
dc.subject | growth | |
dc.subject | inhibitor | |
dc.subject | ligand | |
dc.subject | mutation | |
dc.subject | protein | |
dc.subject | tumor | |
dc.subject | animal experiment | |
dc.subject | animal model | |
dc.subject | animal tissue | |
dc.subject | Article | |
dc.subject | binding affinity | |
dc.subject | cancer inhibition | |
dc.subject | carboxy terminal sequence | |
dc.subject | cell migration | |
dc.subject | colorimetry | |
dc.subject | confocal microscopy | |
dc.subject | controlled study | |
dc.subject | cytoplasm | |
dc.subject | endosome | |
dc.subject | genetic transfection | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | human tissue | |
dc.subject | immunofluorescence test | |
dc.subject | immunoprecipitation | |
dc.subject | lysosome | |
dc.subject | mass spectrometry | |
dc.subject | missense mutation | |
dc.subject | mouse | |
dc.subject | nonhuman | |
dc.subject | protein degradation | |
dc.subject | protein localization | |
dc.subject | protein phosphorylation | |
dc.subject | signal transduction | |
dc.subject | tumor xenograft | |
dc.subject | wild type | |
dc.subject | animal | |
dc.subject | Birt Hogg Dube syndrome | |
dc.subject | C57BL mouse | |
dc.subject | drug screening | |
dc.subject | female | |
dc.subject | genetics | |
dc.subject | kidney tumor | |
dc.subject | male | |
dc.subject | metabolism | |
dc.subject | mutation | |
dc.subject | pathology | |
dc.subject | Schizosaccharomyces | |
dc.subject | transgenic mouse | |
dc.subject | tumor cell line | |
dc.subject | Animals | |
dc.subject | Birt-Hogg-Dube Syndrome | |
dc.subject | Cell Line, Tumor | |
dc.subject | Endosomes | |
dc.subject | ErbB Receptors | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Kidney Neoplasms | |
dc.subject | Male | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Transgenic | |
dc.subject | Mutation | |
dc.subject | Proto-Oncogene Proteins | |
dc.subject | rab GTP-Binding Proteins | |
dc.subject | Schizosaccharomyces | |
dc.subject | Signal Transduction | |
dc.subject | Tumor Suppressor Proteins | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.type | Note | |
dc.contributor.department | DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL) | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1038/ncomms15866 | |
dc.description.sourcetitle | Nature Communications | |
dc.description.volume | 8 | |
dc.description.page | 15866 | |
Appears in Collections: | Elements Staff Publications |
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