Authors
Taoyang Xu, Xueping Luo, Mao Lin, Jiao-Jiao Xu, Li Qiu, Huining Liu, Qier Mu, Tong Yang, Jiaxi Chen, Wangcheng He, Siyuan Ma, Shengyuan Jiang, Jing Yang, Yan He, Can-Can Zheng, Xingyang Xue, Xin Hao, Lian Zhang, Jun Liu, Bin Li, Wenwen Xu
Published in
Cancer research. Aug 05, 2026. Epub Aug 05, 2026.
Abstract
Metastasis remains a leading cause of mortality in esophageal squamous cell carcinoma (ESCC) patients, underscoring the urgent need to elucidate the molecular mechanisms driving disease progression. In this study, we delineated that ZBED2, a zinc finger protein, correlates with inferior survival outcomes and metastasis in ESCC patients. ZBED2 formed phase-separated nuclear condensates that functionally promote tumor metastasis, and integrin-linked kinase (ILK) was pinpointed as a critical downstream effector in mediating the pro-metastatic function of ZBED2. Mechanistically, ZBED2 enhanced the transcription of HSP90AA1, promoted the physical interaction between HSP90AA1 and ILK, and consequently stabilized ILK by suppressing its ubiquitination. Subsequently, ILK promoted PD-L1 transcription and CD8+ T cell exhaustion, thereby creating an immunosuppressive microenvironment that facilitates cancer metastasis. Collectively, these findings establish the pivotal role of ZBED2 in driving ESCC metastasis and immune evasion, thereby validating it as a promising therapeutic target for this aggressive malignancy.
PMID:
42554428
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.
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