School of Dentistry, University of California, Los Angeles, CA 90095, USA.
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90024, USA.
Curr Oncol. 2024 Mar 1;31(3):1311-1322. doi: 10.3390/curroncol31030099.
Head and neck squamous cell carcinoma (HNSCC) refers to the malignancy of squamous cells in the head and neck region. Ranked as the seventh most common cancer worldwide, HNSCC has a very low survival rate, highlighting the importance of finding therapeutic targets for the disease. Integrins are cell surface receptors that play a crucial role in mediating cellular interactions with the extracellular matrix (ECM). Within this protein family, Integrin αV (ITGAV) has received attention for its important functional role in cancer progression. In this study, we first demonstrated the upregulation of expression in HNSCC, with higher expression levels correlating with significantly lower overall survival, based on TCGA (the Cancer Genome Atlas) and GEO datasets. Subsequent in vitro analyses revealed an overexpression of ITGAV in highly invasive HNSCC cell lines UM1 and UMSCC-5 in comparison to low invasive HNSCC cell lines UM2 and UMSCC-6. In addition, knockdown of ITGAV significantly inhibited the migration, invasion, viability, and colony formation of HNSCC cells. In addition, chromatin immunoprecipitation (ChIP) assays indicated that SOX11 bound to the promoter of ITGAV gene, and SOX11 knockdown resulted in decreased ITGAV expression in HNSCC cells. In conclusion, our studies suggest that ITGAV promotes the progression of HNSCC cells and may be regulated by SOX11 in HNSCC cells.
头颈部鳞状细胞癌（HNSCC）是指发生于头颈部区域的鳞状细胞恶性肿瘤。HNSCC 是全球第七大常见癌症，其生存率非常低，这突显了寻找该疾病治疗靶点的重要性。整合素是细胞表面受体，在介导细胞与细胞外基质（ECM）的相互作用中起着至关重要的作用。在这个蛋白家族中，整合素 αV（ITGAV）因其在癌症进展中的重要功能作用而受到关注。在这项研究中，我们首先基于 TCGA（癌症基因组图谱）和 GEO 数据集表明，在 HNSCC 中表达上调，表达水平越高，总生存率越低。随后的体外分析显示，与低侵袭性 HNSCC 细胞系 UM2 和 UMSCC-6 相比，高度侵袭性 HNSCC 细胞系 UM1 和 UMSCC-5 中 ITGAV 过表达。此外，ITGAV 的敲低显著抑制了 HNSCC 细胞的迁移、侵袭、活力和集落形成。此外，染色质免疫沉淀（ChIP）实验表明，SOX11 与 ITGAV 基因的启动子结合，而 SOX11 的敲低导致 HNSCC 细胞中 ITGAV 表达降低。总之，我们的研究表明，ITGAV 促进 HNSCC 细胞的进展，并且可能在 HNSCC 细胞中受到 SOX11 的调控。
