Hu Han, Shen Qi, Zhang Lingfang, Zhu Shuaiqi, Cheng Yining, Duan Haixiao, Zhang Fan, Wang Lin, Jin Yuling, Cao Jinjin, Wang Yang, Liu Binlei
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, College of Bioengineering, Hubei University of Technology, Wuhan, PR China.
Wuhan Binhui Biopharmaceutical Co. Ltd., Wuhan, PR China.
Commun Biol. 2025 Jul 28;8(1):1115. doi: 10.1038/s42003-025-08520-y.
The five-year survival rate for non-small-cell lung cancer (NSCLC) remains poor, primarily due to tumor invasion and metastasis. This study evaluates the anti-metastatic potential of the oncolytic virus OH2 in NSCLC. OH2 inhibits migration and invasion of NSCLC by downregulating β-catenin, as demonstrated in vitro and in a lung metastasis model. OH2 reduces β-catenin mRNA levels, suppressing its transcriptional activity and downstream expression of Matrix Metalloproteinases (MMPs), key mediators of extracellular matrix degradation. Proteomic analysis of the secretome confirms reduced MMPs expression following OH2 treatment. Mechanistically, the OH2 tegument protein UL41 is identified as a critical factor that degrades β-catenin mRNA, thus inhibiting β-catenin nuclear transcriptional activity. These findings reveal a novel anti-metastatic mechanism of OH2 via disruption of the β-catenin/MMPs axis and support its potential as a therapeutic candidate for invasive NSCLC.
非小细胞肺癌（NSCLC）的五年生存率仍然很低，主要原因是肿瘤侵袭和转移。本研究评估了溶瘤病毒OH2在NSCLC中的抗转移潜力。体外实验和肺转移模型表明，OH2通过下调β-连环蛋白抑制NSCLC的迁移和侵袭。OH2降低β-连环蛋白mRNA水平，抑制其转录活性以及细胞外基质降解的关键介质基质金属蛋白酶（MMPs）的下游表达。对分泌蛋白组的蛋白质组学分析证实，OH2处理后MMPs表达降低。从机制上讲，OH2被膜蛋白UL41被确定为降解β-连环蛋白mRNA的关键因子，从而抑制β-连环蛋白的核转录活性。这些发现揭示了OH2通过破坏β-连环蛋白/MMPs轴的新型抗转移机制，并支持其作为侵袭性NSCLC治疗候选药物的潜力。
