磷酸果糖激酶血小板（PFKP）的异常表达通过改变多种生物学功能，在各种人类癌症的发展中发挥着至关重要的作用。然而，PFKP 在头颈鳞状细胞癌 (HNSCC) 中作用的确切分子机制尚未完全阐明。我们评估了 120 名 HNSCC 患者的肿瘤和邻近正常组织中 PFKP 和 c-Myc 的表达水平。进行了一系列体外和体内实验来探索 PFKP 和 c-Myc 之间的反馈回路对 HNSCC 进展的影响。此外，我们利用患者来源的类器官（PDO）、细胞系来源的异种移植物和患者来源的异种移植物探索了靶向 PFKP 和 c-Myc 在 HNSCC 中的治疗效果。我们的研究结果表明，PFKP 在 HNSCC 组织和细胞中频繁上调线，与不良预后相关。我们的体外和体内实验表明，升高的 PFKP 促进 HNSCC 的细胞增殖、血管生成和转移。从机制上讲，PFKP 增加了 ERK 介导的 c-Myc 稳定性，从而推动 HNSCC 的进展。此外，c-Myc 在转录水平刺激 PFKP 表达，从而在 PFKP 和 c-Myc 之间形成正反馈环。此外，我们的多个模型表明，共同靶向 PFKP 和 c-Myc 可在 HNSCC 中引发协同抗肿瘤作用。我们的研究证明了 PFKP/c-Myc 正反馈环在驱动 HNSCC 进展中的关键作用，并表明同时靶向 PFKP c-Myc 可能是一种新颖且有效的 HNSCC 治疗策略。© 2024。作者。

The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated.We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts.Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC.Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.© 2024. The Author(s).