FOXD3 suppresses epithelial-mesenchymal transition through direct transcriptional promotion of SMAD7 in esophageal squamous cell carcinoma
FOXD3 suppresses epithelial-mesenchymal transition through direct transcriptional promotion of SMAD7 in esophageal squamous cell carcinoma
复制标题
FOXD3通过直接转录促进食管鳞状细胞癌中的SMAD7抑制上皮间质转化
DOI：
10.1002/mc.23350
复制
发表时间：
2021
影响因子：
4.6
通讯作者：
Guo Wei
中科院分区：
文献类型：
--
作者：
Wu Zheng;Li Yan;Niu Yunfeng;Lu Juntao;Yan Zhaoyang;Xu Tongxin;Guo Yanli;Dong Zhiming;Guo Wei
转录因子叉头盒D3（FOXD 3）是FOX家族的重要成员，在体内可维持细胞簇、神经嵴和滋养层祖细胞的多能性。研究表明FOXD 3可影响多种肿瘤的增殖、迁移和血管生成，其在生物体中的缺失和过表达无疑会对细胞命运的改变和肿瘤的发生产生重要影响。然而，FOXD 3在食管鳞状细胞癌（ESCC）中的潜在功能和分子机制尚未完全阐明。本研究旨在探讨FOXD 3在食管鳞癌组织中的表达水平及其功能，阐明FOXD 3在食管鳞癌发生发展中的分子机制及预后价值。FOXD 3在食管鳞癌组织和细胞系中的表达水平显著下调，并与患者性别、上消化道癌家族史、TNM分期、浸润深度、淋巴结转移及生存期相关。FOXD 3还可抑制细胞的迁移和侵袭，并参与TGF-β1诱导的上皮-间质转化过程。此外，FOXD 3和SMAD家族成员7（SMAD 7）在ESCC中呈正相关。FOXD 3可直接与SMAD 7基因启动子区结合，导致SMAD 7在人食管癌细胞中的转录促进作用。因此，FOXD 3可能在食管鳞癌中发挥抑癌作用，有望成为食管鳞癌新的治疗靶点和预后指标。
The transcription factor forkhead box D3 (FOXD3) is an important member of the FOX family, which can maintain the pluripotent properties of cell clusters, neural crest, and trophoblastic progenitor cells in vivo. It has been shown that FOXD3 could affect proliferation, migration, and angiogenesis of various tumors and its deletion and overexpression in organisms will undoubtedly have important influence on the change of cell fate and the occurrence of tumors. However, the underlying functions and molecular mechanisms of FOXD3 in esophageal squamous cell carcinoma (ESCC) have not been fully clarified. According to the present study, the expression levels and functional roles of FOXD3 were investigated, and its prognostic value and molecular mechanisms in tumorigenesis and progression of ESCC were clarified. The expression level of FOXD3 was significantly downregulated in ESCC tissues and cell lines, and correlated with gender, family history of upper gastrointestinal cancer, TNM stage, depth of invasion, lymph node metastasis, and ESCC patients' survival. Moreover, FOXD3 inhibited cells migration and invasion as well as participated in TGF‐β1 induced epithelial–mesenchymal transition process. Furthermore, a positive correlation between FOXD3 and SMAD family member 7 (SMAD7) was explored in ESCC. FOXD3 could directly bind to promoter regions ofSMAD7gene, leading to transcriptional promotion of SMAD7 in human esophageal cancer cells. Taken together, FOXD3 may play a tumor suppressor role in ESCC and may be applied as a new therapeutic target and prognostic marker for ESCC.