2. Academic Validation
  3. The Reciprocal Regulation Between TNF-α and Autophagy for Oral Squamous Cell Carcinoma Progression

The Reciprocal Regulation Between TNF-α and Autophagy for Oral Squamous Cell Carcinoma Progression

  • J Oral Pathol Med. 2025 Dec 2. doi: 10.1111/jop.70093.
Chih-Wen Shu 1 2 3,  Chun-Feng Chen 4,  Chia-Che Chang 5,  Cheng-Hsin Lee 3,  Ho-Hsing Tseng 6,  Kai-Fang Hu 7,  Yu-Hsiang Chou 7 8,  Chun-Lin Chen 9,  Wen-Ching Wang 10,  Pei-Feng Liu 3 11 12 13
Affiliations

Affiliations

  • 1 Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
  • 2 Innovation Center for Drug Development and Optimization, National Sun Yat-Sen University, Kaohsiung, Taiwan.
  • 3 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 4 Department of Stomatology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
  • 5 Department of Oncology, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
  • 6 Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 7 Division of Periodontics, Department of Dentistry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 8 School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 9 Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
  • 10 Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
  • 11 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
  • 12 Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 13 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
PMID: 41328537 DOI: 10.1111/jop.70093
Abstract

Background: Autophagy and tumor necrosis factor-alpha (TNF-α) are pivotal in the progression of oral squamous cell carcinoma (OSCC), yet their interplay remains inadequately understood. This study aims to evaluate the interaction between Autophagy and TNF-α for OSCC progression.

Methods: Cytokine levels were measured with the Bio-plex assay; Autophagy activation was visualized by confocal microscopy. NF-κB p65 activity was assessed via reporter assay, and cell growth was evaluated using CellTiter-Glo, clonogenic assay, and flow cytometry. Clinical data were analyzed using SPSS.

Results: The level of TNF-α decreased in OSCC cells treated with an Autophagy inhibitor but increased in OSCC cells under starvation as an autophagy-inducing condition. The production of TNF-α was also lower in OSCC cells knocked down with siULK1 plus siBECN1 or siATG5 plus siATG7 when compared with OSCC cells knocked down with scrambled siRNA under starvation conditions. The addition of TNF-α increased levels of autophagosome and autolysosome in OSCC cells-TNF-α induced expressions of LC3 and p62 by activating RelA. OSCC cells exposed to TNF-α exhibited increased cell viability and Autophagy inhibitors reversed the increased cell viability and growth. TNF-α levels were higher in the serum of OSCC patients than in those with precancerous conditions. Elevated levels of TNF-α were linked to poorer disease-specific survival in OSCC patients. The expression of RelA showed a positive correlation with the expression of LC3 and PP62 in OSCC patients. The increased co-expression of TNF-α/p62, TNF-α/LC3, and TNF-α/RelA/PP62 was associated with shorter disease-free survival in OSCC patients.

Conclusion: The reciprocal regulation between TNF-α and Autophagy may contribute to tumor progression in OSCC.

Keywords

autophagy; cell growth; oral squamous cell carcinoma; prognosis; reciprocal regulation; tumor necrosis factor‐alpha.

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