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

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

  • Mol Cancer. 2024 Jul 9;23(1):141. doi: 10.1186/s12943-024-02051-6.
Weiwei Liu # 1,  Zhao Ding # 1,  Ye Tao # 1,  Shixian Liu # 1,  Maoyu Jiang 1,  Fangzheng Yi 1,  Zixi Wang 2 3,  Yanxun Han 1,  Huaiyuan Zong 2,  Dapeng Li 4,  Yue Zhu 5,  Zihui Xie 1,  Shujia Sang 1,  Xixi Chen 1,  Manli Miao 2,  Xu Chen 2,  Wei Lin 6,  Yi Zhao 1,  Guibin Zheng 7 8,  Mark Zafereo 8,  Guojun Li 8,  Jing Wu 9,  Xiaojun Zha 10 11,  Yehai Liu 12
Affiliations

Affiliations

  • 1 Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
  • 2 Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China.
  • 3 Institutes of Biomedical Sciences, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, Shanghai, 200032, China.
  • 4 Department of Otolaryngology, Head & Neck Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, 236800, China.
  • 5 Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
  • 6 Department of Stomatology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
  • 7 Department of Thyroid Surgery, the Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, 264000, China.
  • 8 Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • 9 Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. wujing@ahmu.edu.cn.
  • 10 Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui Province, 230032, China. zhaxiaojunpumc@gmail.com.
  • 11 Department of Otolaryngology, Head & Neck Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, 236800, China. zhaxiaojunpumc@gmail.com.
  • 12 Department of Otolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. liuyehai@ahmu.edu.cn.
  • # Contributed equally.
PMID: 38982480 DOI: 10.1186/s12943-024-02051-6
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.

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.

Keywords

ERK; HNSCC; PFKP; Tumor progression; c-Myc.

Figures
Products
Inhibitors & Agonists
Other Products