H Tang
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; Marais, R
Authors
L Leung
G Saturno
A Viros
D Smith
G Di Leva
E Morrison
D Niculescu-duvaz
F Lopes
L Johnson
N Dhomen
C Springer
R Marais
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.
Citation
Tang, H., Leung, L., Saturno, G., Viros, A., Smith, D., Di Leva, G., …Marais, R. (2017). Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. Nature communications, 8, 14909. https://doi.org/10.1038/ncomms14909
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 9, 2017 |
Online Publication Date | Apr 18, 2017 |
Publication Date | Apr 18, 2017 |
Deposit Date | Apr 20, 2017 |
Publicly Available Date | Apr 20, 2017 |
Journal | Nature Communications |
Print ISSN | 2041-1723 |
Volume | 8 |
Pages | 14909 |
DOI | https://doi.org/10.1038/ncomms14909 |
Publisher URL | http://dx.doi.org/10.1038/ncomms14909 |
Related Public URLs | https://www.nature.com/ncomms/ |
Additional Information | Funders : Cancer Research UK Manchester Institute;Division of Cancer Therapeutics at The Institute of Cancer Research;Wellcome Trust Grant Number: C5759/A12328 Grant Number: C309/A11566 Grant Number: 1003X, 103021/Z/13/Z, 100282/Z/12/Z |
Files
ncomms14909.pdf
(3.3 Mb)
PDF
Licence
http://creativecommons.org/licenses/by/4.0/
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Downloadable Citations
About USIR
Administrator e-mail: library-research@salford.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search