Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein

Laura A. Laviolette, Julien Mermoud, Isabel A. Calvo, Nicholas Olson, Myriam Boukhali, Ortrud K. Steinlein, Elisabeth Roider, Elke C. Sattler, Dachuan Huang, Bin Tean Teh, Mo Motamedi, Wilhelm Haas and Othon Iliopoulos ()
Additional contact information
Laura A. Laviolette: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Julien Mermoud: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Isabel A. Calvo: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Nicholas Olson: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Myriam Boukhali: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Ortrud K. Steinlein: Institute of Human Genetics, University Hospital Munich, University of Munich
Elisabeth Roider: University Hospital, Ludwig Maximilian University Munich
Elke C. Sattler: University Hospital, Ludwig Maximilian University Munich
Dachuan Huang: Laboratory of Cancer Epigenome, National Cancer Centre Singapore
Bin Tean Teh: Laboratory of Cancer Epigenome, National Cancer Centre Singapore
Mo Motamedi: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Wilhelm Haas: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School
Othon Iliopoulos: Center for Cancer Research, Massachusetts General Hospital Cancer Center and Harvard Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15866 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15866

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15866

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().