Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Division for Health Service Promotion, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
J Pathol. 2018 Oct;246(2):154-165. doi: 10.1002/path.5109. Epub 2018 Aug 13.
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.
小细胞肺癌（SCLC）是一种神经内分泌肿瘤，表现出快速生长和转移扩散。尽管 SCLC 代表一种典型的未分化癌症类型，但甲状腺转录因子-1（TTF-1，基因符号 NKX2-1），一种肺上皮细胞分化和肺形态发生的主调控因子，在这种侵袭性癌症类型中强烈上调。本研究旨在评估 TTF-1 在 SCLC 中的功能作用。我们证明，神经内分泌分化所必需的转录因子achaete-scute complex homolog 1（ASCL1）正向调节 SCLC 细胞系中的 TTF-1。随后，我们描述了可能受 TTF-1 控制的基因和 microRNAs（miRNAs），并确定了核因子 IB（NFIB），这是最近被认为是 SCLC 进展的驱动因素，是 TTF-1 的转录靶点。我们的发现揭示了 SCLC 中由 ASCL1/TTF-1/NFIB 组成的调节轴，可能有助于 SCLC 的肿瘤发生。版权所有 © 2018 英国和爱尔兰病理学会。由 John Wiley & Sons，Ltd 出版。
