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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：磷酸果糖激酶-血小板（PFKP）的异常表达通过修饰多种生物学功能在多种人类癌症的发展中起着至关重要的作用。然而,PFKP在头颈部鳞状细胞癌（HNSCC）中的作用的确切分子机制尚未完全阐明。
方法：我们评估了120例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以探索PFKP和c-Myc之间的反馈回路对HNSCC进展的影响。此外,我们探索了使用患者来源的类器官（PDO）在HNSCC中靶向PFKP和c-Myc的治疗效果，细胞系来源的异种移植物,和患者来源的异种移植物。
结果：我们的发现表明，PFKP在HNSCC组织和细胞系中经常上调，与预后不良有关。我们的体外和体内实验表明，升高的PFKP促进细胞增殖，血管生成,和HNSCC的转移。机械上,PFKP增加了ERK介导的c-Myc的稳定性，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之间形成正反馈回路。此外,我们的多个模型表明，共同靶向PFKP和c-Myc在HNSCC中触发协同抗肿瘤作用。
结论：我们的研究证明了PFKP/c-Myc正反馈回路在驱动HNSCC进展中的关键作用，并提示同时靶向PFKP和c-Myc可能是HNSCC的一种新颖有效的治疗策略。
方法：我们评估了120例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以探索PFKP和c-Myc之间的反馈回路对HNSCC进展的影响。此外,我们探索了使用患者来源的类器官（PDO）在HNSCC中靶向PFKP和c-Myc的治疗效果，细胞系来源的异种移植物,和患者来源的异种移植物。
结果：我们的发现表明，PFKP在HNSCC组织和细胞系中经常上调，与预后不良有关。我们的体外和体内实验表明，升高的PFKP促进细胞增殖，血管生成,和HNSCC的转移。机械上,PFKP增加了ERK介导的c-Myc的稳定性，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之间形成正反馈回路。此外,我们的多个模型表明，共同靶向PFKP和c-Myc在HNSCC中触发协同抗肿瘤作用。
结论：我们的研究证明了PFKP/c-Myc正反馈回路在驱动HNSCC进展中的关键作用，并提示同时靶向PFKP和c-Myc可能是HNSCC的一种新颖有效的治疗策略。
