FOXM1 通过 β-连环蛋白/Tcf4 信号通路诱导食管癌中的血管生成拟态。

FOXM 1 induces Vasculogenic mimicry in esophageal cancer through β-catenin /Tcf4 signaling.

机构信息

Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Changhuai road 287, Bengbu, Anhui, 233000, People's Republic of China.

Department of Pathology, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, Anhui Province, China.

出版信息

Diagn Pathol. 2020 Feb 8;15(1):14. doi: 10.1186/s13000-020-00929-9.

OBJECTIVE

To investigate the role of FOXM1, β-catenin and TCF4 in esophageal cancer (EC) and their relationship to VM (Vasculogenic Mimicry).

METHODS

CCK-8 were performed to examine EC cell proliferation in FOXM1 silenced cells. EC cell migration and invasion were investigated through wound healing and Transwell assays, respectively. The formation of pipe like structures were assessed in 3D cultures. The expression of Foxm1, β-catenin, Tcf4 and E-cadherin were investigated through western blot, RT-qPCR and immunohistochemistry (IHC) staining. The relationship between FOXM1 expression, clinic-pathological features, and overall survival (OS) were further analyzed.

RESULTS

A loss of FOXM1 expression correlated with the OS of ESCC patients. FOXM1 silencing led to a loss of cell growth and suppressed cell migration and invasion in ESCC cells. VM structures were identified in ESCC tissues and human EC cell lines. Mechanistically, FOXM1 was found to promote tumorigenesis through the regulation of β-catenin, Tcf4, and E-cadherin in EC cells, leading to the formation of VM structures.

CONCLUSIONS

These findings highlight FoxM1 as a novel therapeutic target in ESCC.

目的

探讨叉头框蛋白 M1（FOXM1）、β-连环蛋白（β-catenin）和转录因子 4（TCF4）在食管癌（EC）中的作用及其与血管生成拟态（VM）的关系。

方法

通过 CCK-8 法检测沉默 FOXM1 后 EC 细胞的增殖情况。通过划痕愈合和 Transwell 实验分别检测 EC 细胞的迁移和侵袭能力。通过 3D 培养评估管样结构的形成。通过 Western blot、RT-qPCR 和免疫组织化学（IHC）染色检测 Foxm1、β-catenin、Tcf4 和 E-cadherin 的表达。进一步分析 FOXM1 表达与临床病理特征和总生存期（OS）的关系。

结果

FOXM1 表达缺失与 ESCC 患者的 OS 相关。FOXM1 沉默导致 ESCC 细胞的生长丧失，并抑制细胞迁移和侵袭。VM 结构在 ESCC 组织和人 EC 细胞系中被鉴定出来。机制上，FOXM1 被发现通过调节 EC 细胞中的β-catenin、TCF4 和 E-cadherin 促进肿瘤发生，导致 VM 结构的形成。