A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147698 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-4598 (Electronic) Linking ISSN: 14764598 NLM ISO Abbreviation: Mol Cancer Subsets: MEDLINE

Original Publication: [London] : BioMed Central, c2002-

Squamous Cell Carcinoma of Head and Neck*/metabolism ; Squamous Cell Carcinoma of Head and Neck*/pathology ; Squamous Cell Carcinoma of Head and Neck*/genetics ; Proto-Oncogene Proteins c-myc*/metabolism ; Proto-Oncogene Proteins c-myc*/genetics ; Disease Progression* ; Head and Neck Neoplasms*/metabolism ; Head and Neck Neoplasms*/pathology ; Head and Neck Neoplasms*/genetics ; Gene Expression Regulation, Neoplastic* ; Feedback, Physiological*; Humans ; Animals ; Mice ; Cell Line, Tumor ; Phosphofructokinase-1, Type C/metabolism ; Phosphofructokinase-1, Type C/genetics ; Cell Proliferation ; Prognosis ; Female ; Male ; Xenograft Model Antitumor Assays ; Biomarkers, Tumor/metabolism

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.
Conclusion: 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).)

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82303021 Natural Science Foundation of China; 82371133 Natural Science Foundation of China; 82171127 Natural Science Foundation of China; 2208085MH239 Natural Science Foundation of Anhui Province; 2208085MH239 Natural Science Foundation of Anhui Province; NO. 4245 Discipline Construction Project of the First Affiliated Hospital of Anhui Medical University; 2022AH051134 the Natural Science Foundation of Universities of Anhui Province

Keywords: ERK; HNSCC; PFKP; Tumor progression; c-Myc

0 (Proto-Oncogene Proteins c-myc)
EC 2.7.1.- (Phosphofructokinase-1, Type C)
EC 2.7.1.11 (PFKP protein, human)
0 (MYC protein, human)
0 (Biomarkers, Tumor)

Date Created: 20240709 Date Completed: 20240710 Latest Revision: 20240805

20240805

PMC11232239

10.1186/s12943-024-02051-6

38982480