BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial–mesenchymal transition and angiogenesis. (1st May 2021)

• Record Type: Journal Article
• Authors: Zhao, Yan; Gao, Jiajia; Xie, Xiufeng; Nan, Peng; Liu, Fang; Sun, Yulin; Zhao, Xiaohang
• Is Part Of: Cancer medicine. Volume 10:Number 10(2021)
• Page Start: 3413
• Page End: 3426
• Publication Date: 2021-05-01
• Subjects: angiogenesis -- BACH1 -- ESCC -- metastasis -- the EMT; 616.994005
• DOI: 10.1002/cam4.3884
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Metastasis to regional lymph nodes or distal organs predicts the progression of the disease and poor prognosis in esophageal squamous cell carcinoma (ESCC). Previous studies demonstrated that BTB and CNC homology 1 (BACH1) participates in various types of tumor metastasis. However, the function of BACH1 in ESCC was rarely reported. The present study demonstrated that BACH1 protein was overexpressed in ESCC tissues compared with paired esophageal epithelial tissues according to immunohistochemical staining (IHC). Higher levels of BACH1 mRNA were associated with decreased overall survival (OS) and shorter disease‐free survival (DFS) of ESCC patients based on an analysis of The Cancer Genome Atlas (TCGA) datasets. BACH1 significantly enhanced the migration and invasion of ESCC in vitro. Mechanistically, BACH1 promoted the epithelial–mesenchymal transition (EMT) by directly activating the transcription of CDH2, SNAI2, and VIM, as determined by chromatin immunoprecipitation‐quantitative polymerase chain reaction (ChIP‐qPCR). BACH1 overexpression significantly enhanced CDH2 promoter activity according to the results of a luciferase assay. The results of subsequent experiments indicated that BACH1 enhanced the growth of tumor xenografts. The density of CD31 + blood vessels and the expression of vascular endothelial growth factor C (VEGFC) in tumor xenografts were significantly associated with BACH1 levels according to the results of IHC and immunofluorescence (IF) analyses performed in vivo. Moreover, ChIP‐qPCR analysis demonstrated that the transcriptional activity of VEGFC was also upregulated by BACH1. Thus, BACH1 contributes to ESCC metastasis and tumorigenesis by partially facilitating the EMT and angiogenesis, and BACH1 may be a promising therapeutic target or molecular marker in ESCC. Abstract : We investigated the functions of BACH1 in esophageal squamous cell carcinoma (ESCC), and our data firstly demonstrated that BACH1 contributes to ESCC metastasis and progression by EMT and angiogenesis. Substantial evidence supports the view that BACH1 triggers EMT‐induced metastasis by activating CDH2, SNAI2, and VIM transcription in ESCC. BACH1 acts as the upstream regulator to activate CDH2 through binding to its promoter and facilitates angiogenesis partially by activating transcription of VEGFC.