دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: A positive feedback loop between PFKP and c-Myc drives head and neck squamous cell carcinoma progression.
المؤلفون: Liu W; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Ding Z; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Tao Y; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Liu S; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Jiang M; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Yi F; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Wang Z; Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China.; Institutes of Biomedical Sciences, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, 200032, China., Han Y; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Zong H; Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China., Li D; Department of Otolaryngology, Head & Neck Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, 236800, China., Zhu Y; Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Xie Z; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Sang S; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Chen X; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Miao M; Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China., Chen X; Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China., Lin W; Department of Stomatology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Zhao Y; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China., Zheng G; Department of Thyroid Surgery, the Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, 264000, China.; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Zafereo M; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Li G; Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA., Wu J; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. wujing@ahmu.edu.cn., Zha X; Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China. zhaxiaojunpumc@gmail.com.; Department of Otolaryngology, Head & Neck Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, 236800, China. zhaxiaojunpumc@gmail.com., Liu Y; Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. liuyehai@ahmu.edu.cn.
المصدر: Molecular cancer [Mol Cancer] 2024 Jul 09; Vol. 23 (1), pp. 141. Date of Electronic Publication: 2024 Jul 09.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: 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
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2002-
مواضيع طبية MeSH: 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
مستخلص: 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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معلومات مُعتمدة: 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
فهرسة مساهمة: Keywords: ERK; HNSCC; PFKP; Tumor progression; c-Myc
المشرفين على المادة: 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)
تواريخ الأحداث: Date Created: 20240709 Date Completed: 20240710 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC11232239
DOI: 10.1186/s12943-024-02051-6
PMID: 38982480
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4598
DOI:10.1186/s12943-024-02051-6