Cigarette smoke induces epidermal growth factor receptor-dependent redistribution of apical MUC1 and junctional beta-catenin in polarized human airway epithelial cells.

The American Journal of Pathology
Ying-Ting ChenNancy A McNamara

Abstract

Cigarette smoke (CS) accounts for nearly 90% of lung cancer deaths worldwide; however, an incomplete understanding of how CS initiates preneoplastic changes in the normal airway hinders early diagnosis. Short-term exposure to CS causes aberrant activation of epidermal growth factor receptor (EGFR) and canonical Wnt/beta-catenin signaling pathways in human bronchial epithelial (HBE) cells. We hypothesize that this response is elicited through the disruption of spatially segregated cell membrane proteins in the polarized airway epithelium. Using an in vitro model of highly differentiated HBE cells, we observed membrane characteristics consistent with the native airway, including the presence of a membrane mucin, MUC1, at the apical cell pole, beta-catenin at the apical-lateral membrane, and EGFR at the basolateral membrane. Following exposure to smoke, intercellular spaces enlarge and cilia disappear. This histopathology is accompanied by molecular events that include perinuclear trafficking of basolateral EGFR, EGFR phosphorylation, pEGFR-mediated phosphorylation of MUC1's cytoplasmic tail (CT), loss of E-cadherin/beta-catenin complexes at the adherens junctions (AJs), intracellular formation and nuclear shuffling of beta-cateni...Continue Reading

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Citations

Feb 19, 2011·American Journal of Respiratory Cell and Molecular Biology·Dane Parker, Alice Prince
Sep 17, 2014·Head & Face Medicine·Ines WillershausenBrita Willershausen
Nov 29, 2011·Biochemical and Biophysical Research Communications·Lili ZhangNancy A McNamara
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Mar 12, 2015·Biochemical and Biophysical Research Communications·Li ZhaoCai-Yun Zhong
Dec 1, 2017·Journal of Clinical Medicine·Kosuke KatoKwang Chul Kim
Feb 17, 2018·Cell Discovery·Marrah E Lachowicz-ScrogginsJohn V Fahy
Mar 16, 2018·Mediators of Inflammation·Marta Stolarczyk, Bob J Scholte
May 14, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kosuke KatoKwang Chul Kim
Jan 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kosuke KatoK Chul Kim
Jan 24, 2014·American Journal of Physiology. Cell Physiology·Anouk OldenburgerMartina Schmidt
Nov 22, 2018·Respiratory Research·Javier MilaraJulio Cortijo

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