Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.
Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin, 300052, China.
Sci Rep. 2017 May 22;7(1):2229. doi: 10.1038/s41598-017-02494-6.
High mobility group protein A2 (HMGA2) is a transcription factor that plays an important role in the invasion and metastasis of gastric carcinoma (GC). The term vasculogenic mimicry (VM) refers to the unique ability of aggressive tumour cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between HMGA2 and VM formation remains unclear. In the present study, we examined concomitant HMGA2 expression and VM in 228 human GC samples and 4 GC cell lines. Our data indicate that HMGA2 is not only significantly associated with VM formation but also influences the prognosis of patients with gastric carcinoma. Overexpression of HMGA2 significantly increased cell motility, invasiveness, and VM formation both in vitro and in vivo. A luciferase reporter assay, Co-IP and ChIP demonstrated that HMGA2 induced the expression of Twist1 and VE-cadherin by binding to the Twist1 promoter. Moreover, we observed a decrease in VE-cadherin following Twist1 knockdown in cells overexpressing HMGA2. This study indicates that HMGA2 promotes VM in GC via Twist1-VE-cadherin signalling and influences the prognosis of patients with GC.
高迁移率族蛋白 A2（HMGA2）是一种转录因子，在胃癌（GC）的侵袭和转移中发挥重要作用。术语血管生成拟态（VM）是指侵袭性肿瘤细胞模仿胚胎血管生成网络模式的独特能力。然而，HMGA2 与 VM 形成之间的关系尚不清楚。本研究检测了 228 个人 GC 样本和 4 个人 GC 细胞系中 HMGA2 的共表达与 VM。我们的数据表明，HMGA2 不仅与 VM 的形成显著相关，而且还影响胃癌患者的预后。HMGA2 的过表达无论是在体外还是体内均显著增加了细胞的迁移、侵袭和 VM 的形成。荧光素酶报告基因检测、Co-IP 和 ChIP 实验表明，HMGA2 通过与 Twist1 启动子结合诱导 Twist1 和 VE-cadherin 的表达。此外，在过表达 HMGA2 的细胞中敲低 Twist1 后，观察到 VE-cadherin 的减少。本研究表明，HMGA2 通过 Twist1-VE-cadherin 信号通路促进 GC 中的 VM，并影响 GC 患者的预后。
