气候变化领域集成服务门户(CCPortal): Aberrant epithelial polarity cues drive the development of precancerous airway lesions

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DOI	10.1073/pnas.2019282118
	Aberrant epithelial polarity cues drive the development of precancerous airway lesions
	Tilston-Lunel A.; Mazzilli S.; Kingston N.M.; Szymaniak A.D.; Hicks-Berthet J.; Kern J.G.; Abo K.; Reid M.E.; Perdomo C.; Wilson A.A.; Spira A.; Beane J.; Varelas X.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:18
英文摘要	Molecular events that drive the development of precancerous lesions in the bronchial epithelium, which are precursors of lung squamous cell carcinoma (LUSC), are poorly understood. We demonstrate that disruption of epithelial cellular polarity, via the conditional deletion of the apical determinant Crumbs3 (Crb3), initiates and sustains precancerous airway pathology. The loss of Crb3 in adult luminal airway epithelium promotes the uncontrolled activation of the transcriptional regulators YAP and TAZ, which stimulate intrinsic signals that promote epithelial cell plasticity and paracrine signals that induce basal-like cell growth. We show that aberrant polarity and YAP/TAZ-regulated gene expression associates with human bronchial precancer pathology and disease progression. Analyses of YAP/TAZ-regulated genes further identified the ERBB receptor ligand Neuregulin-1 (NRG1) as a key transcriptional target and therapeutic targeting of ERBB receptors as a means of preventing and treating precancerous cell growth. Our observations offer important molecular insight into the etiology of LUSC and provides directions for potential interception strategies of lung cancer. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Epithelial polarity; Lung basal cells; Lung precancer; YAP/TAZ
语种	英语
scopus关键词	Crumbs3 protein; dacomitinib; epidermal growth factor receptor; membrane protein; neu differentiation factor; tamoxifen; transcription factor Yap1; unclassified drug; Crb3 protein, mouse; epidermal growth factor receptor; membrane protein; neu differentiation factor; adult; airway epithelium cell; animal cell; animal experiment; animal model; animal tissue; Article; basal cell; bronchus biopsy; bronchus epithelium; cell growth; cell plasticity; cell polarity; clinical article; cohort analysis; controlled study; disease exacerbation; disease severity; gene deletion; gene expression regulation; genetic transcription; human; human cell; human tissue; lung cancer; mouse; nonhuman; observational study; paracrine signaling; pathology; phosphorylation; precancer; priority journal; regulator gene; squamous cell lung carcinoma; TAZ gene; YAP gene; cell polarity; epithelium; epithelium cell; genetics; lung tumor; metabolism; precancer; signal transduction; squamous cell carcinoma; Carcinoma, Squamous Cell; Cell Polarity; Epithelial Cells; Epithelium; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Membrane Glycoproteins; Neuregulin-1; Precancerous Conditions; Signal Transduction; Transcriptional Coactivator with PDZ-Binding Motif Proteins; YAP-Signaling Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251193
作者单位	Department of Biochemistry, Boston University, School of Medicine, Boston, MA 02118, United States; Department of Medicine, Boston University, School of Medicine, Boston, MA 02118, United States; Center for Regenerative Medicine of Boston University, Boston Medical Center, Boston, MA 02118, United States; Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, United States; Pulmonary Center, Boston University, School of Medicine, Boston, MA 02118, United States; Lung Cancer Initiative (LCI), Johnson and Johnson, Cambridge, MA 02142, United States
推荐引用方式 GB/T 7714	Tilston-Lunel A.,Mazzilli S.,Kingston N.M.,et al. Aberrant epithelial polarity cues drive the development of precancerous airway lesions[J],2021,118(18).
APA	Tilston-Lunel A..,Mazzilli S..,Kingston N.M..,Szymaniak A.D..,Hicks-Berthet J..,...&Varelas X..(2021).Aberrant epithelial polarity cues drive the development of precancerous airway lesions.Proceedings of the National Academy of Sciences of the United States of America,118(18).
MLA	Tilston-Lunel A.,et al."Aberrant epithelial polarity cues drive the development of precancerous airway lesions".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021).