Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.
Smith, Duncan L
Di Leva, Gianpiero
AffiliationMolecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester M20 4BX
MetadataShow full item record
AbstractLysyl 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.
CitationLysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. 2017, 8:14909 Nat Commun
- Lysyl oxidase promotes liver metastasis of gastric cancer via facilitating the reciprocal interactions between tumor cells and cancer associated fibroblasts.
- Authors: Li Q, Zhu CC, Ni B, Zhang ZZ, Jiang SH, Hu LP, Wang X, Zhang XX, Huang PQ, Yang Q, Li J, Gu JR, Xu J, Luo KQ, Zhao G, Zhang ZG
- Issue date: 2019 Nov
- The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats.
- Authors: Miana M, Galán M, Martínez-Martínez E, Varona S, Jurado-López R, Bausa-Miranda B, Antequera A, Luaces M, Martínez-González J, Rodríguez C, Cachofeiro V
- Issue date: 2015 Jun
- Intracellular lysyl oxidase: effect of a specific inhibitor on nuclear mass in proliferating cells.
- Authors: Saad FA, Torres M, Wang H, Graham L
- Issue date: 2010 Jun 11
- Lysyl oxidase is essential for hypoxia-induced metastasis.
- Authors: Erler JT, Bennewith KL, Nicolau M, Dornhöfer N, Kong C, Le QT, Chi JT, Jeffrey SS, Giaccia AJ
- Issue date: 2006 Apr 27
- Lysyl oxidase contributes to mechanotransduction-mediated regulation of transforming growth factor-β signaling in breast cancer cells.
- Authors: Taylor MA, Amin JD, Kirschmann DA, Schiemann WP
- Issue date: 2011 May