Division of Oncology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Comprehensive Cancer Center, Spitalgasse 23, 1090 Vienna, Austria.
Int J Mol Sci. 2022 Jan 19;23(3):1050. doi: 10.3390/ijms23031050.
Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor prognosis. So far, the EGFR inhibitor cetuximab is the only approved targeted therapy. A deeper understanding of the molecular and genetic basis of HNSCC is needed to identify additional targets for rationally designed, personalized therapeutics. The transcription factor EVI1, the major product of the locus, is an oncoprotein with roles in both hematological and solid tumors. In HNSCC, high EVI1 expression was associated with an increased propensity to form lymph node metastases, but its effects in this tumor entity have not yet been determined experimentally. We therefore overexpressed or knocked down in several HNSCC cell lines and determined the impact of these manipulations on parameters relevant to tumor growth and invasiveness, and on gene expression patterns. Our results revealed that promoted the proliferation and migration of HNSCC cells. Furthermore, it augmented tumor spheroid formation and the ability of tumor spheroids to displace an endothelial cell layer. Finally, altered the expression of numerous genes in HNSCC cells, which were enriched for Gene Ontology terms related to its cellular functions. In summary, represents a novel oncogene in HNSCC that contributes to cellular proliferation and invasiveness.
头颈部鳞状细胞癌（HNSCC）是一种常见的恶性肿瘤，预后不良。到目前为止，EGFR 抑制剂西妥昔单抗是唯一批准的靶向治疗药物。为了确定合理设计的个体化治疗的其他靶点，需要更深入地了解 HNSCC 的分子和遗传基础。转录因子 EVI1 是 基因座的主要产物，是一种在血液系统和实体瘤中均发挥作用的癌蛋白。在 HNSCC 中，EVI1 高表达与形成淋巴结转移的倾向增加有关，但它在这种肿瘤实体中的作用尚未通过实验确定。因此，我们在几种 HNSCC 细胞系中过表达或敲低了 ，并确定了这些操作对与肿瘤生长和侵袭性相关的参数以及基因表达模式的影响。我们的结果表明， 促进了 HNSCC 细胞的增殖和迁移。此外，它增强了肿瘤球体的形成以及肿瘤球体取代内皮细胞层的能力。最后， 改变了 HNSCC 细胞中许多基因的表达，这些基因在功能上与它的细胞功能相关的基因本体论术语富集。总之， 是 HNSCC 中的一种新的癌基因，它促进细胞增殖和侵袭。
