Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

Wnt 信号传导是参与器官发育、肿瘤发生和癌症进展的关键途径。 WNT7A 是 Wnt 家族的成员，但对其在头颈鳞状细胞癌 (HNSCC) 中的作用及其潜在分子机制仍知之甚少。根据癌症基因组图谱（TCGA）、HNSCC的转录组测序数据，发现肿瘤中WNT7A的表达水平高于邻近正常组织，并通过实时RT-PCR和免疫组化进行了验证。出乎意料的是，WNT7A 的过度表达并没有激活 HNSCC 中的经典 Wnt-β-catenin 通路。相反，我们的研究结果表明，WNT7A 可能激活 FZD7/JAK1/STAT3 信号通路，从而增强细胞增殖、自我更新和抗凋亡能力。此外，在患者来源的异种移植（PDX）肿瘤模型中，观察到WNT7A和磷酸化STAT3的高表达，这与肿瘤进展呈正相关。这些发现强调了 WNT7A 在 HNSCC 进展中的重要性，并提出靶向 FZD7/JAK1/STAT3 通路中的关键分子作为精确治疗 HNSCC 的有前途的策略。