NCF2在食管鳞状细胞癌中通过NR2F2/LATS2/YAP1轴驱动肿瘤进展和转移。

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-07-09 DOI:10.1016/j.canlet.2025.217902

Huan Zhang , Zhaokai Wang , Naicheng Song , Ang Xiao , Yaxuan Liu , Ai Huang , Zuhuan Yao , Zhihong Huang , Quanchao Sun , Yue Qu , Shijie Xing , Li Wan , Qingfeng Zheng , Lei Huang , Ke Jiang

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引用次数: 0

摘要

发生淋巴结转移是食管鳞状细胞癌（ESCC）预后不良的重要因素，主要是因为其治疗后复发风险高。然而，ESCC淋巴转移的生物学机制尚不清楚。在这里，我们发现NCF2异常过表达，并与ESCC患者的不良预后相关。NCF2表达失调以ros不依赖的方式促进ESCC的进展和淋巴转移。NCF2直接与NR2F2相互作用，阻断其核易位，导致LATS2下调，激活YAP1及其靶基因，从而促进ESCC的肿瘤发生、淋巴管生成和转移。本研究证实NCF2/NR2F2/LATS2/YAP1轴在ESCC的肿瘤发生和转移中起重要作用，提示NCF2可能是ESCC的一个有吸引力的治疗靶点和预后标志物。

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NCF2 drives tumor progression and metastasis through NR2F2/LATS2/YAP1 axis in esophageal squamous cell carcinoma

The occurrence of lymph node spread is the major significant factor associated with esophageal squamous cell carcinoma (ESCC)'s poor prognosis, mainly because of its association with a high risk of recurrence after treatment. However, the biological mechanisms underlying lymphatic metastasis in ESCC are not well recognized. Here, we show that NCF2 is aberrantly overexpressed and is associated with poor prognosis in patients with ESCC. Dysregulation of NCF2 expression promotes ESCC progression and lymphatic metastasis in a ROS-independent manner. NCF2 directly interacts with NR2F2 and blocks its nuclear translocation, which can result in the downregulation of LATS2 and the activation of YAP1 and its target genes and thereby promote tumorigenesis, lymphangiogenesis and metastasis in ESCC. This study establishes that the NCF2/NR2F2/LATS2/YAP1 axis plays a vital role in tumorigenesis and metastasis, suggesting that NCF2 may serve as an attractive therapeutic target and prognostic marker in ESCC.

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.