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Cell Rep. 2016 Jul 19;16(3):631-43. doi: 10.1016/j.celrep.2016.06.020. Epub 2016 Jun 30.

Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients.

Author information

1
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
2
Division of Pathology, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
3
Division of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
4
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands; Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
5
Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
6
Core Facility for Molecular Pathology and Biobanking, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
7
Division of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
8
Mouse Clinic for Cancer and Aging research Transgenic Core Facility, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
9
Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands.
10
Mouse Clinic for Cancer and Aging research Transgenic Core Facility, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands. Electronic address: i.huijbers@nki.nl.
11
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam 1066 CX, the Netherlands; Skolkovo Institute of Science and Technology, Moscow 143026, Russia. Electronic address: a.berns@nki.nl.

Abstract

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1)-negative invasive tumor cell population. Consistent with the mouse data, we find that NFIB is overexpressed in almost all tested human metastatic high-grade neuroendocrine lung tumors, warranting further assessment of NFIB as a tumor progression marker in a clinical setting.

PMID:
27373156
PMCID:
PMC4956617
DOI:
10.1016/j.celrep.2016.06.020
[Indexed for MEDLINE]
Free PMC Article

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