The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Stomatology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China.
Int J Med Sci. 2020 Jun 27;17(11):1598-1609. doi: 10.7150/ijms.46809. eCollection 2020.
ATPase family AAA domain-containing protein 2 (ATAD2) is highly expressed in a variety of malignancies and can promote the proliferation of tumor cells and inhibit their differentiation. However, the expression of ATAD2 and its related mechanism in oral squamous cell carcinoma (OSCC) are still unknown. Immunohistochemical staining of ATAD2, cancer stem cells (CSCs) markers and immune checkpoint molecules was conducted on human OSCC specimens to determine the expression levels of these proteins and their correlations with the clinicopathological characteristics of ATAD2 in OSCC. Moreover, the role of ATAD2 in cell proliferation, apoptosis, migration and epithelial-mesenchymal transition (EMT) were assessed by silencing ATAD2 . Immunohistochemical analysis revealed that ATAD2 expression in OSCC tissues was markedly higher than that in adjacent dysplastic tissues and normal mucosal tissues. Overexpression of ATAD2 was related to poor overall survival in OSCC patients. In addition, the protein expression of ATAD2 was notably correlated with the expression of B7-H4, PD-L1, CMTM6, Slug and ALDH1 in human OSCC. ATAD2 knockdown arrested the cell cycle, promoted the apoptosis, and inhibited the proliferation, migration, and EMT of OSCC cells. In conclusion, these findings revealed that ATAD2 is highly expressed in OSCC and can act as a poor prognostic indicator.
ATP 酶家族 AAA 结构域包含蛋白 2(ATAD2)在多种恶性肿瘤中高表达,可促进肿瘤细胞的增殖,抑制其分化。然而,ATAD2 在口腔鳞状细胞癌(OSCC)中的表达及其相关机制尚不清楚。通过免疫组织化学染色检测 ATAD2、癌症干细胞(CSCs)标志物和免疫检查点分子在人 OSCC 标本中的表达水平,以确定这些蛋白的表达水平及其与 OSCC 中 ATAD2 的临床病理特征的相关性。此外,通过沉默 ATAD2 评估 ATAD2 在细胞增殖、凋亡、迁移和上皮-间充质转化(EMT)中的作用。免疫组织化学分析显示,ATAD2 在 OSCC 组织中的表达明显高于相邻异型增生组织和正常黏膜组织。ATAD2 的过表达与 OSCC 患者的总生存不良相关。此外,ATAD2 的蛋白表达与人类 OSCC 中 B7-H4、PD-L1、CMTM6、Slug 和 ALDH1 的表达显著相关。ATAD2 敲低可使细胞周期停滞,促进细胞凋亡,并抑制 OSCC 细胞的增殖、迁移和 EMT。综上所述,这些发现表明 ATAD2 在 OSCC 中高表达,可作为不良预后的指标。