The mechanism of transcription factor GATA3 in esophageal squamous cell carcinoma

GATA3 is a transcription factor.In this study, a comprehensive analysis of whole transcriptome data from ESCC and adjacent tissues revealed a significant enrichment of GATA3 and its regulatory pathway in ESCC.Validation from multiple ESCC gene expression datasets confirmed the upregulation of GATA3, underscoring its pivotal role in ESCC.Subsequent functional experiments further substantiated that GATA3 plays a crucial role in promoting the proliferation of ESCC cells both in vitro and in vivo.To further elucidate the molecular mechanisms, ChIP-seq was performed to define the GATA3 cistrome.The enriched motif was discovered by MEME.The differential expressed genes were analyzed by whole-transcriptome sequencing.Interactions between GATA3 and co-factors were verified with co-immunoprecipitation.The binding of GATA3 and co-factors at same genomic location was examined by sequential ChIP.The transcriptional regulation of GATA3 on target genes was validated by ChIP-qPCR, RT-qPCR and Western Blot.Clinical sample analysis indicated that the high transcriptional activity of the GATA3/ATF4/target gene regulatory axis not only closely correlates with the degree of malignancy in tumor cells but also exhibits a significant association with the activation of cancer-associated fibroblasts (CAFs), suggesting a potential oncogenic role for this regulatory axis, likely through its modulation of tumormicroenvironment interactions.In summary, this study revealed the critical roles of GATA3 in driving the malignant phenotypes of ESCC.We systematically elucidated the molecular mechanisms by which the GATA3/ATF4/target gene regulatory axis drive the proliferation of ESCC cells.This finding provides new potential therapeutic targets for ESCC patients and is expected to serve as an important basis for the development of novel targeted treatment strategies for ESCC.