Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface

Tang, H, Leung, L, Saturno, G, Viros, A, Smith, D, Di Leva, G, Morrison, E, Niculescu-duvaz, D, Lopes, F, Johnson, L, Dhomen, N, Springer, C and Marais, R 2017, 'Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface' , Nature Communications, 8 .

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Abstract

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.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing
ISSN: 2041-1723
Related URLs:
Funders: Cancer Research UK Manchester Institute, Division of Cancer Therapeutics at The Institute of Cancer Research, Wellcome Trust
Depositing User: G Di Leva
Date Deposited: 20 Apr 2017 11:57
Last Modified: 08 Aug 2017 11:11
URI: http://usir.salford.ac.uk/id/eprint/42157

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