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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 orcid ; 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
; ; ; ; ; ; ; and
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 Inc.
external identifiers
  • pmid:29876935
  • 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
2024-06-24 20:26:33
@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}},
  keywords     = {{ASCL1; neuroendocrine differentiation; NFIB; SCLC; TTF-1}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{154--165}},
  publisher    = {{John Wiley & Sons Inc.}},
  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}},
  doi          = {{10.1002/path.5109}},
  volume       = {{246}},
  year         = {{2018}},
}