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.

中文翻译：

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转录因子FOXM1调节头颈部鳞状细胞癌的增殖与异常分化之间的平衡。

FOXM1的持续表达是几乎所有人类癌症的标志，包括头颈部鳞状细胞癌（HNSCC）。HNSCCs部分保留上皮分化程序，该程序概括了肿瘤起源组织的胎儿和成年特征，但由于遗传改变和肿瘤支持途径而受到调节。使用shRNA介导的敲低，我们证明了在标准细胞培养条件下，FOXM1对HNSCC细胞系增殖和迁移的影响最小。但是，在三维（3D）培养和异种移植肿瘤模型中，FOXM1的敲低导致增殖减少，侵袭减少和分化程度更高的表型，表明HNSCC细胞中FOXM1活性的背景依赖性调节。通过在HNSCC细胞系中异位表达FOXM1，我们证明减少表达的皮肤型角蛋白K1和囊蛋白作为鳞状分化的标志物，支持FOXM1在HNSCC中异常分化的调控中的作用。因此，我们的数据为针对HNSCC中的FOXM1提供了有力的依据。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版