Co-expression analysis reveals mechanisms underlying the varied roles of NOTCH1 in non-small cell lung cancer,Journal of Thoracic Oncology

当前位置： X-MOL 学术 › J. Thorac. Oncol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Co-expression analysis reveals mechanisms underlying the varied roles of NOTCH1 in non-small cell lung cancer
Journal of Thoracic Oncology ( IF 20.4 ) Pub Date : 2019-02-01 , DOI: 10.1016/j.jtho.2018.10.162
Sara L Sinicropi-Yao ₁ , Joseph M Amann ₂ , David Lopez Y Lopez ₂ , Ferdinando Cerciello ₃ , Kevin R Coombes ₄ , David P Carbone ₂

Affiliation

Introduction: Notch receptor family dysregulation can be tumor promoting or suppressing depending on cellular context. Our studies shed light on the mechanistic differences that are responsible for NOTCH1’s opposing roles in lung adenocarcinoma and lung squamous cell carcinoma. Methods: We integrated transcriptional patient‐derived datasets with gene co‐expression analyses to elucidate mechanisms behind NOTCH1 function in subsets of NSCLC. Differential co‐expression was examined using hierarchical clustering and principal component analysis. Enrichment analysis was used to examine pathways associated with the underlying transcriptional networks. These pathways were validated in vitro and in vivo. Endogenously epitope‐tagged NOTCH1 was used to identify novel interacting proteins. Results: NOTCH1 co‐expressed genes in lung adenocarcinoma and squamous carcinoma were distinct and associated with either angiogenesis and immune system pathways or cell cycle control and mitosis pathways, respectively. Tissue culture and xenograft studies of lung adenocarcinoma and lung squamous models with NOTCH1 knockdown showed growth differences and opposing effects on these pathways. Differential NOTCH1 interacting proteins were identified as potential mediators of these differences. Conclusions: Recognition of the opposing role of NOTCH1 in lung cancer, downstream pathways, and interacting proteins in each context may help direct the development of rational NOTCH1 pathway‐dependent targeted therapies for specific tumor subsets of NSCLC.

更新日期：2019-02-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>