The transcription factor FOXM1 regulates the balance between proliferation and aberrant differentiation in head and neck squamous cell carcinoma.

Details

Serval ID
serval:BIB_0EE0AF2ED71C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The transcription factor FOXM1 regulates the balance between proliferation and aberrant differentiation in head and neck squamous cell carcinoma.
Journal
The Journal of pathology
Author(s)
Roh V., Hiou-Feige A., Misetic V., Rivals J.P., Sponarova J., Teh M.T., Ferreira Lopes S., Truan Z., Mermod M., Monnier Y., Hess J., Tolstonog G.V., Simon C.
ISSN
1096-9896 (Electronic)
ISSN-L
0022-3417
Publication state
Published
Issued date
01/2020
Peer-reviewed
Oui
Volume
250
Number
1
Pages
107-119
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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-mediated 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. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Keywords
Animals, Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Female, Forkhead Box Protein M1/genetics, Forkhead Box Protein M1/metabolism, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms/genetics, Head and Neck Neoplasms/metabolism, Head and Neck Neoplasms/pathology, Humans, Mice, Nude, Signal Transduction, Squamous Cell Carcinoma of Head and Neck/genetics, Squamous Cell Carcinoma of Head and Neck/metabolism, Squamous Cell Carcinoma of Head and Neck/pathology, Tumor Burden, FOXM1, head and neck cancer, invasion, squamous differentiation
Pubmed
Web of science
Open Access
Yes
Create date
24/09/2019 12:31
Last modification date
09/07/2020 5:22
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