Yang Kai, Li Yanshi, Song Kai, Pan Min, Lu Tao, Wang Mengna, Cheng Zhaobo, Hu Guohua, Wen Tongling, Wang Min, Chen Tao
Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Department of Otolaryngology, The People's Hospital of Anshun City, Anshun City, 561000, Guizhou, China.
Med Oncol. 2025 Jun 3;42(7):236. doi: 10.1007/s12032-025-02789-z.
Lymphatic metastasis (LM) remains a major contributor to mortality among patients with head and neck squamous cell carcinoma (HNSCC). Understanding the molecular mechanisms underlying LM and identifying novel therapeutic targets are critical priorities. This study investigated ADAM22, a protein implicated in cell adhesion, migration, and differentiation, for its role in HNSCC and its association with LM. Its expression levels were evaluated in HNSCC tissues with and without LM using quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry. The prognostic relevance of ADAM22 was analyzed through Kaplan-Meier survival curves and Cox proportional hazards models. Functional assays, including EdU incorporation, flow cytometry, wound healing, and Transwell migration assays, were performed in FADU and SCC15 cell lines alongside an in vivo footpad xenograft mouse model. ADAM22 was found to be significantly overexpressed in HNSCC cases with LM. In vitro, silencing of ADAM22 suppressed tumor cell proliferation, migration, and invasion and promoted apoptosis. Both in vitro and in vivo experiments demonstrated that ADAM22 enhances tumor growth and lymphatic spread by promoting epithelial-mesenchymal transition (EMT). Further analysis identified integrins as key mediators in ADAM22-driven EMT and metastasis. In summary, these findings indicate that ADAM22 promotes LM in HNSCC by regulating EMT through integrin signaling, highlighting its potential as a therapeutic target and providing new perspectives for diagnosing and treating HNSCC.
淋巴转移（LM）仍然是头颈部鳞状细胞癌（HNSCC）患者死亡的主要原因。了解LM背后的分子机制并确定新的治疗靶点是关键优先事项。本研究调查了与细胞黏附、迁移和分化有关的蛋白质ADAM22在HNSCC中的作用及其与LM的关联。使用定量实时PCR（qRT-PCR）、蛋白质免疫印迹法和免疫组织化学评估了有或无LM的HNSCC组织中ADAM22的表达水平。通过Kaplan-Meier生存曲线和Cox比例风险模型分析了ADAM22的预后相关性。在FADU和SCC15细胞系以及体内足垫异种移植小鼠模型中进行了包括EdU掺入、流式细胞术、伤口愈合和Transwell迁移试验在内的功能试验。发现ADAM22在伴有LM的HNSCC病例中显著过表达。在体外，沉默ADAM22可抑制肿瘤细胞增殖、迁移和侵袭并促进细胞凋亡。体外和体内实验均表明，ADAM22通过促进上皮-间质转化（EMT）增强肿瘤生长和淋巴扩散。进一步分析确定整合素是ADAM22驱动的EMT和转移的关键介质。总之，这些发现表明，ADAM22通过整合素信号通路调节EMT促进HNSCC中的LM，突出了其作为治疗靶点的潜力，并为HNSCC的诊断和治疗提供了新的视角。
