BATF condensation drives gastric cancer metastasis via chromatin association and transcriptional regulation

While liquid-liquid phase separation (LLPS) is understood to be relevant with various types of cancers, the relationship between LLPS and gastric cancer (GC) remains ambiguous. In this study, we demonstrate that the basic leucine zipper ATF-like transcription factor (BATF) shows increased DNA-binding activity and expression in GC tissues and cell lines, based on assay for transposase-accessible chromatin sequencing (ATAC-seq) and RNA sequencing (RNA-seq) analyses. Additionally, in GC cells, BATF forms droplet-like nuclear condensates. Using combined approaches of chromatin immunoprecipitation sequencing (ChIP-seq), ATAC-seq, and RNA-seq, we find that BATF condensation promotes its binding to the TM4SF1 promoter and enhancer regions, thereby regulating TM4SF1 transcription and prompting the TM4SF1-driven formation of focal adhesions and GC metastasis. Thus, we unveil a role for BATF LLPS in GC metastasis through its modulation of chromatin association and transcriptional regulation, highlighting the relevance of LLPS to GC progression and potential treatment approaches.