RRC ID 54114
Author Horie M, Miyashita N, Mattsson JSM, Mikami Y, Sandelin M, Brunnström H, Micke P, Nagase T, Saito A.
Title An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.
Journal J. Pathol.
Abstract Small cell lung cancer (SCLC) is a neuroendocrine tumour that exhibits rapid growth and metastatic spread. Although SCLC represents a prototypically undifferentiated cancer type, thyroid transcription factor-1 (TTF-1, gene symbol NKX2-1), a master regulator for pulmonary epithelial cell differentiation and lung morphogenesis, is strongly upregulated in this aggressive cancer type. The aim of this study was to evaluate a functional role for TTF-1 in SCLC. We demonstrated that achaete-scute complex homolog 1 (ASCL1), an essential transcription factor for neuroendocrine differentiation, positively regulated TTF-1 in SCLC cell lines. Subsequently, we described genes and microRNAs (miRNAs) that were possibly controlled by TTF-1 and identified nuclear factor IB (NFIB), a recently characterised driver of SCLC progression, as a transcriptional target of TTF-1. Our findings shine light on a regulatory axis in SCLC consisting of ASCL1/TTF-1/NFIB that potentially contributes to the tumourigenesis of SCLC. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Volume 246(2)
Pages 154-165
Published 2018-10
DOI 10.1002/path.5109
PMID 29876935
MeSH Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism Cell Differentiation Cell Line, Tumor Databases, Genetic Female Gene Expression Profiling / methods* Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / genetics* Lung Neoplasms / metabolism Lung Neoplasms / pathology Male MicroRNAs / genetics MicroRNAs / metabolism NFI Transcription Factors / genetics NFI Transcription Factors / metabolism Prognosis Signal Transduction Small Cell Lung Carcinoma / genetics* Small Cell Lung Carcinoma / metabolism Small Cell Lung Carcinoma / pathology Thyroid Nuclear Factor 1 / genetics* Thyroid Nuclear Factor 1 / metabolism* Transcription, Genetic Transcriptome*
IF 6.253
Human and Animal Cells Lu-134-A(RCB0466) Lu-134-B(RCB0467) Lu-139(RCB0469)