This research investigates the molecular drivers of esophageal squamous cell carcinoma (ESCC), focusing on how liquid-liquid phase separation (LLPS) regulates tumor progression. By optimizing genomic sequencing techniques for small clinical samples, the authors identify TFAP2β as a critical transcription factor that is significantly reduced in early-stage cancer tissues. The study demonstrates that TFAP2β acts as a tumor suppressor by forming biomolecular condensates that recruit other proteins to repress the expression of the oncogene ZNF131. To translate these findings into a clinical context, the researchers identified a small molecule compound named A6 that restores these regulatory functions by promoting TFAP2β condensation. Experimental results across cell lines, animal models, and patient-derived organoids confirm that this drug effectively inhibits cancer cell growth and metastasis. Ultimately, the work establishes a new therapeutic strategy for treating ESCC by targeting the physical phase-separation properties of transcriptional regulators.

References:

• Deng Z, Pu L, Deng K, et al. Targeting TFAP2β condensation suppresses the development of esophageal squamous cell carcinoma[J]. Cell, 2025.