Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.
Authors
Tang, HaoranLeung, L
Saturno, Grazia
Viros, Amaya
Smith, Duncan L
Di Leva, Gianpiero
Morrison, Eamonn
Niculescu-Duvaz, D
Lopes, F
Johnson, L
Dhomen, Nathalie
Springer, Caroline
Marais, Richard
Affiliation
Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester M20 4BXIssue Date
2017-04-18
Metadata
Show full item recordAbstract
Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623.Citation
Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. 2017, 8:14909 Nat CommunJournal
Nature CommunicationsDOI
10.1038/ncomms14909PubMed ID
28416796Type
ArticleLanguage
enISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/ncomms14909