TY  - JOUR
AU  - Roh, Vincent
AU  - Hiou-Feige, Agnès
AU  - Misetic, Vinko
AU  - Rivals, Jean-Paul
AU  - Sponarova, Jana
AU  - Teh, Muy-Teck
AU  - Ferreira Lopes, Silvia
AU  - Truan, Zinnia
AU  - Mermod, Maxime
AU  - Monnier, Yan
AU  - Hess, Jochen
AU  - Tolstonog, Genrich V
AU  - Simon, Christian
TI  - The transcription factor FOXM1 regulates the balance between proliferation and aberrant differentiation in head and neck squamous cell carcinoma.
JO  - The journal of pathology
VL  - 250
IS  - 1
SN  - 1096-9896
CY  - Bognor Regis [u.a.]
PB  - Wiley
M1  - DKFZ-2019-02140
SP  - 107-119
PY  - 2020
N1  - 2020 Jan;250(1):107-119
AB  - Sustained expression of FOXM1 is a hallmark of nearly all human cancers including squamous cell carcinomas of the head and neck (HNSCC). HNSCCs partially preserve the epithelial differentiation program, which recapitulates fetal and adult traits of the tissue of tumor origin but is deregulated by genetic alterations and tumor-supporting pathways. Using shRNA-induced knockdown, we demonstrate a minimal impact of FOXM1 on proliferation and migration of HNSCC cell lines under standard cell culture conditions. However, FOXM1 knockdown in three-dimensional (3D) culture and xenograft tumor models resulted in reduced proliferation, decreased invasion and a more differentiated-like phenotype, indicating a context dependent modulation of FOXM1 activity in HNSCC cells. By ectopic overexpression of FOXM1 in HNSCC cell lines, we demonstrate a reduced expression of cutaneous-type keratin K1 and involucrin as a marker of squamous differentiation, supporting the role of FOXM1 in modulation of aberrant differentiation in HNSCC. Thus, our data provide a strong rationale for targeting FOXM1 in HNSCC. This article is protected by copyright. All rights reserved.
LB  - PUB:(DE-HGF)16
C6  - pmid:31465124
DO  - DOI:10.1002/path.5342
UR  - https://inrepo02.dkfz.de/record/144698
ER  -