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https://doi.org/10.1038/ncomms15866
| Title: | Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein | Authors: | 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. |
Keywords: | afatinib early endosome antigen 1 epidermal growth factor receptor estrone guanosine triphosphatase activating protein immunoglobulin G antibody lysosome associated membrane protein 1 protein kinase B rab7a protein scatter factor scatter factor receptor STAT3 protein tumor suppressor protein unclassified drug EGFR protein, human epidermal growth factor receptor FLCN protein, human oncoprotein Rab protein Rab7 protein tumor suppressor protein anatomy cancer cells and cell components enzyme enzyme activity gene gene expression growth inhibitor ligand mutation protein tumor animal experiment animal model animal tissue Article binding affinity cancer inhibition carboxy terminal sequence cell migration colorimetry confocal microscopy controlled study cytoplasm endosome genetic transfection human human cell human tissue immunofluorescence test immunoprecipitation lysosome mass spectrometry missense mutation mouse nonhuman protein degradation protein localization protein phosphorylation signal transduction tumor xenograft wild type animal Birt Hogg Dube syndrome C57BL mouse drug screening female genetics kidney tumor male metabolism mutation pathology Schizosaccharomyces transgenic mouse tumor cell line Animals Birt-Hogg-Dube Syndrome Cell Line, Tumor Endosomes ErbB Receptors Female Humans Kidney Neoplasms Male Mice, Inbred C57BL Mice, Transgenic Mutation Proto-Oncogene Proteins rab GTP-Binding Proteins Schizosaccharomyces Signal Transduction Tumor Suppressor Proteins Xenograft Model Antitumor Assays |
Issue Date: | 2017 | Publisher: | Nature Publishing Group | 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 | 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. | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/174490 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms15866 |
| Appears in Collections: | Elements Staff Publications |
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