FOXA2 modulates the proliferation and metastasis of esophageal squamous cell carcinoma by suppressing proteasome activity

Background Esophageal squamous cell carcinoma (ESCC) represents a highly lethal malignancy. The FOXA2 was involved in cellular proliferation, differentiation, tumorigenesis, and metastasis. The precise regulatory mechanisms of FOXA2 in ESCC progression remain unclear. Materials and methods Western blotting, reverse transcription-quantitative polymerase chain reaction, and immunohistochemistry were used to detect the expression level of FOXA2, CCK-8, transwell, and wound healing assays in vitro and xenograft tumor model in vivo were applied to assess the function of FOXA2. RNA-Seq analysis and the following functional assays were used to elucidate the relationship between FOXA2 and proteasome activity. Results The expression level of FOXA2 was downregulated in ECSS tissues and cells. Overexpression of FOXA2 in ESCC cells inhibited epithelial-mesenchymal transition in ESCC cells with the upregulation of E-cadherin and downregulation of Vimentin. Meanwhile, overexpression of FOXA2 inhibited the proliferation, migration, and invasion of ESCC cells. Mechanically, proteasome was involved in the ESCC cells proliferation and invasion inhibition induced by FOXA2, and reduced proteasome activity inhibited ESCC cells proliferation and invasion. Conclusion FOXA2 inhibited the proliferation and invasion of ESCC cells by regulating proteasome activity. FOXA2 plays a critical role in ESCC progression and may act as a potential candidate target for ESCC treatment.