dc.contributor.author | Tang, H | |
dc.contributor.author | Leung, L | |
dc.contributor.author | Saturno, G | |
dc.contributor.author | Viros, A | |
dc.contributor.author | Smith, D | |
dc.contributor.author | Di Leva, G | |
dc.contributor.author | Morrison, E | |
dc.contributor.author | Niculescu-Duvaz, D | |
dc.contributor.author | Lopes, F | |
dc.contributor.author | Johnson, L | |
dc.contributor.author | Dhomen, N | |
dc.contributor.author | Springer, C | |
dc.contributor.author | Marais, R | |
dc.date.accessioned | 2017-05-02T10:06:03Z | |
dc.date.issued | 2017-04-18 | |
dc.identifier.citation | Nature communications, 2017, 8 pp. 14909 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/625 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/ncomms14909 | |
dc.description.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. | |
dc.format | Electronic | |
dc.format.extent | 14909 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Membrane | |
dc.subject | Animals | |
dc.subject | Dogs | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Rats | |
dc.subject | Neoplasms | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Disease Progression | |
dc.subject | Aminopropionitrile | |
dc.subject | Epidermal Growth Factor | |
dc.subject | Protein-Lysine 6-Oxidase | |
dc.subject | Enzyme Inhibitors | |
dc.subject | Biosensing Techniques | |
dc.subject | Signal Transduction | |
dc.subject | Cell Proliferation | |
dc.subject | Enzyme Activation | |
dc.subject | Models, Biological | |
dc.subject | Transforming Growth Factor beta1 | |
dc.subject | Matrilin Proteins | |
dc.subject | ErbB Receptors | |
dc.subject | High-Temperature Requirement A Serine Peptidase 1 | |
dc.title | Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-02-09 | |
rioxxterms.versionofrecord | 10.1038/ncomms14909 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-04-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting | |
pubs.publication-status | Published | |
pubs.volume | 8 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Gene & Oncogene Targeting | |
dc.contributor.icrauthor | Springer, Caroline | |