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An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer

Horie, Masafumi; Miyashita, Naoya; Mattsson, Johanna Sofia Margareta; Mikami, Yu; Sandelin, Martin; Brunnström, Hans LU ; Micke, Patrick; Nagase, Takahide and Saito, Akira (2018) In Journal of Pathology 246(2). p.154-165
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ASCL1, neuroendocrine differentiation, NFIB, SCLC, TTF-1
in
Journal of Pathology
volume
246
issue
2
pages
12 pages
publisher
John Wiley & Sons
external identifiers
  • scopus:85052371089
ISSN
0022-3417
DOI
10.1002/path.5109
language
English
LU publication?
yes
id
b7698c87-b8c1-402b-a031-af682b41e252
date added to LUP
2018-10-05 10:06:36
date last changed
2019-02-20 11:29:01
@article{b7698c87-b8c1-402b-a031-af682b41e252,
  abstract     = {<p>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.</p>},
  author       = {Horie, Masafumi and Miyashita, Naoya and Mattsson, Johanna Sofia Margareta and Mikami, Yu and Sandelin, Martin and Brunnström, Hans and Micke, Patrick and Nagase, Takahide and Saito, Akira},
  issn         = {0022-3417},
  keyword      = {ASCL1,neuroendocrine differentiation,NFIB,SCLC,TTF-1},
  language     = {eng},
  number       = {2},
  pages        = {154--165},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Pathology},
  title        = {An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer},
  url          = {http://dx.doi.org/10.1002/path.5109},
  volume       = {246},
  year         = {2018},
}