四川大学华西医院最新Cell论文：揭开液-液体相分离抑制食管鳞癌的新机制，提出相分离靶向疗法

Core Viewpoint - The study reveals a novel mechanism of transcriptional regulation mediated by liquid-liquid phase separation (LLPS) in esophageal squamous cell carcinoma (ESCC), providing potential new strategies for its treatment [3][10]. Group 1: Research Findings - The research identifies transcription factor TFAP2β as a key downregulated transcription factor in ESCC, which suppresses the expression of ZNF131 through LLPS, thereby inhibiting ESCC progression [2][7]. - Two additional downregulated transcription factors, NFIX and ID4, are recruited to the TFAP2β condensate, enhancing its DNA binding capability, indicating that LLPS may be a common feature in the transcriptional regulation of ESCC [8][10]. - The study successfully improved the ATAC-seq technique for clinical samples, achieving a library preparation success rate of over 80% for ESCC and other gastrointestinal tumors [7]. Group 2: Therapeutic Implications - A small molecule compound A6 was identified through virtual screening, which enhances TFAP2β condensation and exhibits specific anti-tumor effects in ESCC models while minimally affecting normal esophageal cells [8][10]. - The findings suggest that targeting transcription factor phase separation could represent a novel therapeutic strategy for ESCC, addressing the urgent need for specific targeted therapies in this cancer type [6][10]. Group 3: Context of ESCC - ESCC accounts for approximately 90% of all esophageal cancer cases and is associated with a high mortality rate globally, highlighting the critical need for effective treatment options [5]. - Current treatment options for ESCC, including surgery, radiotherapy, and chemotherapy, often have limited efficacy and significant side effects, underscoring the necessity for personalized and targeted therapies [6].