肿瘤侵袭和转移是口腔鳞状细胞癌（OSCC）高死亡率的根本原因。能量代谢重编程已被认为是介导肿瘤转移的关键过程，因此迫切需要深入研究肿瘤能量代谢的具体机制。在这里，我们鉴定了一种 RNA 结合蛋白 DAZ 相关蛋白 1 (DAZAP1)，它是一种肿瘤促进因子，在 OSCC 进展中发挥重要作用。 DAZAP1在OSCC中显着上调，增强OSCC细胞的迁移和侵袭并诱导上皮间质转化（EMT）。 RNA-seq 分析和实验验证表明 DAZAP1 调节 OSCC 中的线粒体能量代谢。从机制上讲，DAZAP1经过液-液相分离（LLPS）在细胞核中积累，通过调节前mRNA选择性剪接增强细胞色素c氧化酶16（COX16）表达，从而促进OSCC侵袭和线粒体呼吸。在小鼠 OSCC 模型中，DAZAP1 的缺失会抑制 EMT、下调 COX16 并减少肿瘤生长和转移。在 OSCC 患者样本中，DAZAP1 的表达与 COX16 呈正相关，两种蛋白的高表达与患者预后不良相关。总之，这些发现揭示了 DAZAP1 支持线粒体代谢和 OSCC 肿瘤发展的机制，表明针对 DAZAP1 的治疗策略具有阻止 OSCC 侵袭和转移的潜力。

Tumor invasion and metastasis are the underlying causes of the high mortality rate of oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhanced cytochrome-c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In OSCC patient samples, expression of DAZAP1 positively correlated with COX16, and high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.