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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Masafumi Horie
  • Naoya Miyashita
  • Johanna Sofia Margareta Mattsson
  • Yu Mikami
  • Martin Sandelin
  • Hans Brunnström
  • Patrick Micke
  • Takahide Nagase
  • Akira Saito
Enheter & grupper
Externa organisationer
  • University of Tokyo
  • Uppsala universitet
  • Regional Laboratories Region Skåne
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Sidor (från-till)154-165
Antal sidor12
TidskriftJournal of Pathology
Volym246
Utgåva nummer2
StatusPublished - 2018
PublikationskategoriForskning
Peer review utfördJa