ZBED2的相分离稳定ILK以驱动食管鳞状细胞癌的转移和免疫逃逸

Phase Separation of ZBED2 Stabilizes ILK to Drive Metastasis and Immune Evasion in Esophageal Squamous Cell Carcinoma.

期刊: Cancer Research
PMID: 42554428
原文: PubMed ↗
发布日期: 2026-08-05

作者

Taoyang Xu — Guangzhou Medical University Guangzhou, Guangdong China.
Xueping Luo — Guangzhou Medical University Guangzhou, Guangdong China.
Mao Lin — Guangzhou Medical University Guangzhou, Guangdong China.
Jiao-Jiao Xu — Guangzhou Medical University Guangzhou China.
Li Qiu — First Affiliated Hospital of Guangzhou Medical University China.
Huining Liu — First Affiliated Hospital of Hebei Medical University Shijiazhuang China.
Qier Mu — Guangzhou Medical University guangzhou China.
Tong Yang — Guangzhou Medical University Guangzhou, Guangdong China.
Jiaxi Chen — Guangzhou Medical University Guangzhou, Guangdong China.
Wangcheng He — Guangzhou Medical University Guangzhou, Guangdong China.
Siyuan Ma — Guangzhou Medical University Guangzhou, Guangdong China.
Shengyuan Jiang — Guangzhou Medical University Guangzhou, Guangdong China.
Jing Yang — Guangzhou Medical University Guangzhou China.
Yan He — Guangzhou Medical University Guangzhou, Guangdong China.
Can-Can Zheng — Guangzhou Medical University Guangzhou, Guangdong China.
Xingyang Xue — First Affiliated Hospital of Guangzhou Medical University Guangzhou China.
Xin Hao — Yancheng Institute of Technology China.
Lian Zhang — First Affiliated Hospital of Hebei Medical University China.
Jun Liu — First Affiliated Hospital of Guangzhou Medical University Guangzhou China.
Bin Li — Guangzhou Medical University Guangzhou, Guangdong China.
Wenwen Xu — Guangzhou Medical University Guangzhou, Guangdong China.

作者单位

Guangzhou Medical University Guangzhou, Guangdong China.
Guangzhou Medical University Guangzhou China.
First Affiliated Hospital of Guangzhou Medical University China.
First Affiliated Hospital of Hebei Medical University Shijiazhuang China.
Guangzhou Medical University guangzhou China.
First Affiliated Hospital of Guangzhou Medical University Guangzhou China.
Yancheng Institute of Technology China.
First Affiliated Hospital of Hebei Medical University China.

摘要

中文

转移仍然是食管鳞状细胞癌（ESCC）患者死亡的主要原因，迫切需要阐明驱动疾病进展的分子机制。在本研究中，我们描述了锌指蛋白ZBED2与ESCC患者较差的生存结局和转移相关。ZBED2形成相分离核凝聚体，功能上促进肿瘤转移，并确定整合素连接激酶（ILK）是介导ZBED2促转移功能的关键下游效应因子。机制上，ZBED2增强HSP90AA1的转录，促进HSP90AA1与ILK的物理相互作用，从而通过抑制ILK泛素化来稳定ILK。随后，ILK促进PD-L1转录和CD8+ T细胞耗竭，从而创造促进癌症转移的免疫抑制微环境。总之，这些发现确立了ZBED2在驱动ESCC转移和免疫逃逸中的关键作用，从而验证其作为这种侵袭性恶性肿瘤的有前景治疗靶点。

English

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.

分类与指标

研究类型: 基础研究
病种: 食管癌
JCR 分区: Q1
影响因子: 22.6
新锐分区: 1区