Neoplasma. 2016;63(6):846-855. doi: 10.4149/neo_2016_603.
Colorectal cancer is one of the most common malignant tumors with a high rate of distant metastasis, postoperative recurrence and mortality. ATPase family AAA domain-containing protein 2 (ATAD2), a member of ATPase family, is highly expressed in various cancers, including colorectal cancer. However, whether ATAD2 plays a role in the migration and invasion of colorectal cancer cells remains unknown. In this study, we established ATAD2 knockdown in colorectal cancer cell lines by RNA interference and found that silencing of ATAD2 inhibited the migration and invasion ability of Caco-2 and SW-480 cells. Moreover, ATAD2 silencing suppressed epithelial-mesenchymal transition (EMT), and reduced the expression and enzymatic activity of matrix metalloproteinases (MMPs) in Caco-2 and SW-480 cells. In summary, our results suggest that silencing of ATAD2 inhibits migration and invasion of colorectal cancer cells by suppressing EMT and decreasing the activity of MMPs. Hence, ATAD2 could be considered as a novel molecular marker of metastatic colorectal cancer, and it may provide new insights for clinical diagnosis and treatment of colorectal cancer.
结直肠癌是最常见的恶性肿瘤之一,具有较高的远处转移、术后复发和死亡率。ATP 酶家族 AAA 结构域包含蛋白 2(ATAD2)是 ATP 酶家族的成员,在多种癌症中高表达,包括结直肠癌。然而,ATAD2 是否在结直肠癌细胞的迁移和侵袭中发挥作用尚不清楚。在本研究中,我们通过 RNA 干扰在结直肠癌细胞系中建立了 ATAD2 敲低,发现沉默 ATAD2 抑制了 Caco-2 和 SW-480 细胞的迁移和侵袭能力。此外,ATAD2 沉默抑制上皮-间充质转化(EMT),并降低 Caco-2 和 SW-480 细胞中基质金属蛋白酶(MMPs)的表达和酶活性。综上所述,我们的研究结果表明,沉默 ATAD2 通过抑制 EMT 和降低 MMPs 的活性抑制结直肠癌细胞的迁移和侵袭。因此,ATAD2 可以被认为是转移性结直肠癌的新型分子标志物,它可能为结直肠癌的临床诊断和治疗提供新的见解。