Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, Taiyuan, China.
Department of Infection, Shanxi Provincial People's Hospital, Taiyuan, China.
Gene. 2022 May 25;824:146406. doi: 10.1016/j.gene.2022.146406. Epub 2022 Mar 8.
Esophageal squamous cell carcinoma (ESCC) is one type of the most common malignancies, yet the overall survival rate is still not ideal. IQ motif containing GTPase activating protein 1 (IQGAP1) participates in cell biological functions of various tumors as an oncogene. However, the mechanisms of IQGAP1 affecting malignant development of ESCC are still unclear. In this study, the expression and correlation of IQGAP1 and MMP2 in esophageal cancer tissues were evaluated by online databases and immunohistochemistry. Stably transfected cell lines with IQGAP1 overexpression and knockdown were constructed. Cell growth, migration and invasion ability, the expression of MMP2 and NF-κB expression were examined in ESCC cells. Furthermore, the cellular malignant phenotypes of ESCC and MMP2 expression in IQGAP1 overexpressing cells after treatment with the NF-κB inhibitor pyrrolidinecarbodithioic acid (PDTC) or JSH-23 were detected. We found that the expression of IQGAP1 and MMP2 were up-regulated and positively correlated in ESCC tissues. IQGAP1 overexpression promoted the growth, migration and invasion of ESCC cells, and up-regulated the expression of MMP2, and increased the expression and the nuclear localization level of NF-κB. Treating with PDTC or JSH-23 reversed IQGAP1-mediated cell migration and invasion ability, as well as the expression of MMP2. In summary, IQGAP1 plays a tumor promotion role to regulate the migration and invasion of ESCC cells and the expression of MMP2 through upregulating NF-κB activity, supporting a promising therapeutic target against ESCC.
食管鳞状细胞癌 (ESCC) 是最常见的恶性肿瘤之一，但总体生存率仍不理想。IQ motif 含有 GTPase 激活蛋白 1 (IQGAP1) 作为一种癌基因，参与各种肿瘤的细胞生物学功能。然而，IQGAP1 影响 ESCC 恶性发展的机制尚不清楚。在这项研究中，通过在线数据库和免疫组织化学评估了 IQGAP1 和 MMP2 在食管癌组织中的表达和相关性。构建了 IQGAP1 过表达和敲低的稳定转染细胞系。在 ESCC 细胞中检测细胞生长、迁移和侵袭能力、MMP2 和 NF-κB 表达的变化。此外，检测了 IQGAP1 过表达细胞中 MMP2 表达和 NF-κB 抑制剂吡咯烷二硫代羧酸 (PDTC) 或 JSH-23 处理后 ESCC 的细胞恶性表型。结果发现，IQGAP1 和 MMP2 的表达在 ESCC 组织中上调且呈正相关。IQGAP1 过表达促进 ESCC 细胞的生长、迁移和侵袭，并上调 MMP2 的表达，增加 NF-κB 的表达和核定位水平。用 PDTC 或 JSH-23 处理可逆转 IQGAP1 介导的细胞迁移和侵袭能力以及 MMP2 的表达。总之，IQGAP1 通过上调 NF-κB 活性发挥肿瘤促进作用，调节 ESCC 细胞的迁移和侵袭以及 MMP2 的表达，为 ESCC 的治疗提供了有希望的靶点。
