FoXA2 promotes esophageal squamous cell carcinoma progression by ZEB2 activation

Hanjing Gao,Yanfang Chen,Haiyan Sun,Zheng Yan

doi:10.1186/s12957-021-02358-4

Abstract

BackgroundIt has been reported that Forkhead transcription family member (FOXA2) regulates esophageal squamous cell carcinoma (ESCC) progression. However, the specific mechanism, by which FOXA2 promotes ESCC malignant progression, remains unclear.Materials and methodsQRT-PCR and western blotting were applied to measure FOXA2 expression in ESCC tissues, while CCK-8 assay and Transwell assays were used to investigate the effect of FOXA2 on ESCC. Luciferase reporter assay, followed by fast chromatin immunoprecipitation (ChIP) assay, was used to study the relationship between FOXA2 and ZEB2.ResultsFOXA2 was significantly increased in ESCC tissues, when compared to normal tissues. Moreover, high expression of FOXA2 was also found in ESCC cells. Knockdown of FOXA2 inhibited ESCC cell proliferation, invasion, and migration. Mechanically, FOXA2 was verified to regulate ZEB2 expression at transcription level. Moreover, ZEB2 reversed the inhibitory effect of FOXA2 on ESCC proliferation, invasion, and migration. The relationship between ZEB2 and FOXA2 in ESCC tissues was negative.ConclusionsThese results indicate that FOXA2 plays a critical role in ESCC progression and may become a potential candidate target for ESCC treatment.

Highlights

Esophageal cancer is one of the most common malignant tumors, with the incidence rate ranks third, and the cancer-related mortality rate ranks fourth in China [1, 2]
These results indicate that Forkhead box protein A2 (FOXA2) plays a critical role in esophageal squamous cell carcinoma (ESCC) progression and may become a potential candidate target for ESCC treatment
FOXA2 was highly expressed in human ESCC tissues and cells The expression of FOXA2 in ESCC tissues was detected by qRT-PCR and western blotting

Summary

Introduction

Esophageal cancer is one of the most common malignant tumors, with the incidence rate ranks third, and the cancer-related mortality rate ranks fourth in China [1, 2]. Esophageal squamous cell carcinoma (ESCC) is the most histologic type [3,4,5]. Accumulating evidence indicate that the dysregulation of FOXA2 is related to the development of various cancers [11,12,13]. It has been reported that downregulation of FOXA2 promoted the ability of migration and invasion in lung cancer [14]. Downregulation of FOXA2 enhanced the metastasis of pancreatic cancer by regulating the epithelial-to-mesenchymal transition (EMT) [16]. It has been reported that Forkhead transcription family member (FOXA2) regulates esophageal squamous cell carcinoma (ESCC) progression. The specific mechanism, by which FOXA2 promotes ESCC malignant progression, remains unclear

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