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Abnormal phase separation drives new progress in the research field of esophageal cancer

02 Mar,2026

According to the website of the National Natural Science Foundation of China, Professor Jiang Hao, Professor Yang Jinlin, Professor Yang Li, and Researcher Ke Bowen from Sichuan University, together with institutions such as the University of Oxford in the UK, have made new progress in the field of phase separation anomaly driven esophageal cancer research. The study has revealed the condensation mechanism of key transcription factors in esophageal squamous cell carcinoma. The research findings, titled "Intervention Study on the Evolution of Esophageal Squamous Cell Carcinoma Targeting TFAP2 β Agglomerates," were published online on December 16, 2025 in the journal Cell.
Esophageal cancer is a common malignant tumor of the digestive tract, mainly divided into esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. Esophageal squamous cell carcinoma accounts for about 90% of cases of esophageal cancer, and is a malignant tumor with high incidence rate and mortality in China and even in the world. There is currently no clinically applicable specific targeted therapy drug for esophageal squamous cell carcinoma, and there is a lack of precise molecular level targeted intervention methods and drugs. Clinical treatment mainly relies on surgery, radiotherapy, chemotherapy, and broad-spectrum immunotherapy, with limited efficacy and urgent need for improvement in patient prognosis.
The research team optimized the library construction process and conducted high-quality chromatin accessibility and transcriptome analysis to systematically analyze the transcriptional regulation abnormalities that occur in early esophageal squamous cell carcinoma. They identified and revealed that the transcription factor TFAP2 β is significantly downregulated in esophageal squamous cell carcinoma cells and is a key tumor suppressor for early cell carcinogenesis. Further research has shown that TFAP2 β negatively regulates the expression of downstream core gene ZNF131 and regulates the progression of esophageal squamous cell carcinoma by inhibiting the recruitment of transcription regulatory factor YAP1 through the formation of nuclear aggregates driven by liquid-liquid phase separation. The research team further discovered through virtual screening that the small molecule compound A6 can specifically promote the phase separation behavior of TFAP2 β and exhibit significant anti-tumor activity in cell, mouse, and human organoid models.
This study proposes a treatment strategy for esophageal squamous cell carcinoma by regulating transcription factor phase separation through small molecules, and obtains candidate compounds for targeted transcription factor phase separation in esophageal squamous cell carcinoma treatment, providing ideas and basis for related research and clinical translation.

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