2. Academic Validation
  3. F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production

F. nucleatum facilitates oral squamous cell carcinoma progression via GLUT1-driven lactate production

  • EBioMedicine. 2023 Jan 27;88:104444. doi: 10.1016/j.ebiom.2023.104444.
Jiwei Sun 1,  Qingming Tang 1,  Shaoling Yu 1,  Mengru Xie 1,  Wenhao Zheng 1,  Guangjin Chen 1,  Ying Yin 1,  Xiaofei Huang 1,  Keqi Wo 1,  Haoqi Lei 1,  Junyuan Zhang 1,  Qian Wan 2,  Lili Chen 3
Affiliations

Affiliations

  • 1 Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China.
  • 2 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, Hubei, China; Institute of Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, Hubei, China.
  • 3 Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China. Electronic address: chenlili1030@hust.edu.cn.
PMID: 36709580 DOI: 10.1016/j.ebiom.2023.104444
Abstract

Background: Tumor-resident microbiota has been documented for various Cancer types. Oral squamous cell carcinoma (OSCC) is also enriched with microbiota, while the significance of microbiota in shaping the OSCC microenvironment remains elusive.

Methods: We used bioinformatics and clinical sample analysis to explore relationship between F. nucleatum and OSCC progression. Xenograft tumor model, metabolic screening and RNA Sequencing were performed to elucidate mechanisms of pro-tumor role of F. nucleatum.

Findings: We show that a major protumorigenic bacterium, F. nucleatum, accumulates in invasive margins of OSCC tissues and drives tumor-associated macrophages (TAMs) formation. The mechanistic dissection shows that OSCC-resident F. nucleatum triggers the GalNAc-Autophagy-TBC1D5 signaling, leading to GLUT1 aggregation in the plasma membrane and the deposition of extracellular lactate. Simultaneous functional inhibition of GalNAc and GLUT1 efficiently reduces TAMs formation and restrains OSCC progression.

Interpretation: These findings suggest that tumor-resident microbiota affects the immunomodulatory and protumorigenic microenvironment via modulating glycolysis and extracellular lactate deposition. The targeted intervention of this process could provide a distinct clinical strategy for patients with advanced OSCC.

Funding: This work was supported by the National Natural Science Foundation of China for Key Program Projects (82030070, to LC) and Distinguished Young Scholars (31725011, to LC), as well as Innovation Team Project of Hubei Province (2020CFA014, to LC).

Keywords

Autophagy; F. nucleatum; GLUT1; Oral squamous cell carcinoma; Tumor-associated macrophage.

Figures
Products