Department of Otolaryngology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China.
Department of Anesthesiology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China.
J Cell Biochem. 2018 May;119(5):3864-3872. doi: 10.1002/jcb.26494. Epub 2018 Jan 22.
Nasopharyngeal carcinoma (NPC) is frequently seen in Chinese, especially the population that resides in southeast China. Metastasis-associated protein 1 (MTA1) is a chromatin modifier and plays a role in tumor cell metastasis. IQGAP1 is a ubiquitously expressed protein that contributes to cytoskeleton remodeling. This study aimed to investigate the role of MTA1 and IQGAP1 in NPC malignant transformation. MTA1 and IQGAP1 expression in NPC (n = 43) and control tissues (n = 31) were detected using qRT-PCR, immunoblot, and immunohistochemistry. MTA1 was overexpressed in CNE-1 and CNE-2 cell line by pcDNA3.1/MTA1 transfection. Dominant-negative p53 was transfected to inhibit p53 activity. si-IQGAP1 or dominant-negative IQGAP1 (IQGAP1ΔGRD) was used to suppress IQGAP1 activity. Cell proliferation was measured by CKK-8 assay. Cell migration was evaluated by Transwell assay. The results showed that MTA1 and IQGAP1 were highly expressed in NPC tissues compared with the controls. Forced expression of MTA1 accelerated cell proliferation and migration and upregulated IQGAP1 expression in a p53-independent way. Knockdown of IQGAP1 or transfection of dominant-negative IQGAP1 impeded tumor cell proliferation and migration as well as PI3K/Akt signaling induced by MTA1. In conclusion, MTA1 participates in NPC malignant transformation via regulating IQGAP1 expression and PI3K/Akt signaling pathway.
鼻咽癌（NPC）在中国较为常见，尤其是在中国东南部的人群中。转移相关蛋白 1（MTA1）是一种染色质修饰物，在肿瘤细胞转移中发挥作用。IQGAP1 是一种广泛表达的蛋白，有助于细胞骨架重塑。本研究旨在探讨 MTA1 和 IQGAP1 在 NPC 恶性转化中的作用。使用 qRT-PCR、免疫印迹和免疫组织化学检测 NPC（n=43）和对照组织（n=31）中的 MTA1 和 IQGAP1 表达。通过 pcDNA3.1/MTA1 转染在 CNE-1 和 CNE-2 细胞系中过表达 MTA1。转染显性失活 p53 以抑制 p53 活性。使用 si-IQGAP1 或显性失活 IQGAP1（IQGAP1ΔGRD）抑制 IQGAP1 活性。通过 CKK-8 测定法测量细胞增殖。通过 Transwell 测定法评估细胞迁移。结果表明，与对照组相比，MTA1 和 IQGAP1 在 NPC 组织中高表达。强制表达 MTA1 以 p53 非依赖性方式加速细胞增殖和迁移，并上调 IQGAP1 表达。敲低 IQGAP1 或转染显性失活 IQGAP1 可阻止肿瘤细胞增殖和迁移，以及 MTA1 诱导的 PI3K/Akt 信号通路。总之，MTA1 通过调节 IQGAP1 表达和 PI3K/Akt 信号通路参与 NPC 恶性转化。
