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- W1920765900 abstract "Lung cancers are a leading cause of death worldwide, and although there is someevidence that both Epidermal Growth Factor Receptor (EGFR) and Wnt/β-cateninsignalling are involved in initiation and progression of this disease the molecularmechanisms regulating these processes remain poorly described. Here I show that deletionof LRIG1, an endogenous EGFR inhibitor, leads to epithelial hyperplasia in the murineairway and continued proliferation post confluence in vitro. This occurs viaphosphorylation of EGFR and its downstream effector molecule ERK1/2. Human lungcancer cell lines lacking LRIG1 showed a reduction of proliferation on LRIG1replacement. Using co-localisation experiments I have defined LRIG1 inhibition ofdensity dependent growth occurs through LRIG1 forming a complex with EGFR andE-Cadherin at the cell confluence. Examination of matched human pre-invasive lungcancer lesions with normal airway from the same individuals delineated loss of LRIG1supporting its role in the early stages of cancer development.I further show that β-catenin regulates epithelial cell phenotype in both normal airwaystem cells and preinvasive lung cancers. β-catenin inhibition within keratin 14-expressingstem cells impairs airway repair whilst activation increases cell proliferation, directslineage choice, and promotes an epithelial-to-mesenchymal transition that includes loss ofcadherin-mediated adhesions and increased Twist and Snail transcription influencing both intercellular and cell-matrix adhesiveness. These findings were recapitulated in vitro bothby pharmacological β-catenin activation and direct E-cadherin inhibition. Thus,β-catenin modulation of cadherin-dependent intercellular adhesions determines cellphenotype and its overexpression is a key early step in pre-invasive disease development." @default.
- W1920765900 created "2016-06-24" @default.
- W1920765900 creator A5073876921 @default.
- W1920765900 date "2011-10-28" @default.
- W1920765900 modified "2023-09-26" @default.
- W1920765900 title "EGFR and WNT/β-catenin signalling in airway homeostasis and repair" @default.
- W1920765900 hasPublicationYear "2011" @default.
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