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Article Open Access

Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR

  • Authors:
    • Yu-Hao Huang
    • Peng-Ju Chien
    • Wen-Ling Wang
    • Li-Sung Hsu
    • Yen-Min Huang
    • Wen-Wei Chang
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402306, Taiwan, R.O.C., Institute of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan, R.O.C., Division of Hematology and Oncology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Chang Gung Medical Foundation, Keelung 204201, Taiwan, R.O.C.
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 44
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    Published online on: January 9, 2025
       https://doi.org/10.3892/ijmm.2025.5485
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Abstract

Oral squamous cell carcinoma (OSCC) is a type of head and neck cancer (HNC) with a high recurrence rate, which has been reported to be associated with the presence of cancer stem cells (CSCs). Tribbles pseudokinase 3 (TRIB3) is involved in intracellular signaling and the aim of the present study was to investigate the role of TRIB3 in the maintenance of CSCs. Analysis of The Cancer Genome Atlas database samples demonstrated a positive correlation between TRIB3 expression levels and shorter overall survival rates in patients with HNC. Knockdown of TRIB3 in the SAS and HSC-3 OSCC cell lines reduced cell proliferation through the induction of cell cycle arrest, but not of apoptosis. The population of OSCC-CSCs, defined by a high level of intracellular aldehyde dehydrogenase activity and the ability to form tumorspheres, was also reduced in TRIB3-silenced OSCC cells. The tumorigenicity of tumorspheres derived from the SAS OSCC cell line was reduced following TRIB3 knockdown. These results suggested the potential involvement of TRIB3 in the self-renewal capability of the OSCC CSCs. Mechanistically, TRIB3 was shown to positively regulate SOX2 expression via maintaining both the protein expression level and the SOX2 promoter-binding capability of E2F transcription factor 1 (E2F1). Additionally, TRIB3 also increased the expression level of EGFR through preventing its lysosomal degradation. The significant associations between TRIB3 and E2F1, SOX2 or EGFR expression were also confirmed using a HNC tissue array. Taken together, the findings of the present study may suggest that TRIB3 is an oncogenic protein that supports the stemness of OSCC and that targeting TRIB3 may be a potential strategy for OSCC therapy in the future.
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Copy and paste a formatted citation
Spandidos Publications style
Huang Y, Chien P, Wang W, Hsu L, Huang Y and Chang W: Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR. Int J Mol Med 55: 44, 2025.
APA
Huang, Y., Chien, P., Wang, W., Hsu, L., Huang, Y., & Chang, W. (2025). Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR. International Journal of Molecular Medicine, 55, 44. https://doi.org/10.3892/ijmm.2025.5485
MLA
Huang, Y., Chien, P., Wang, W., Hsu, L., Huang, Y., Chang, W."Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR". International Journal of Molecular Medicine 55.3 (2025): 44.
Chicago
Huang, Y., Chien, P., Wang, W., Hsu, L., Huang, Y., Chang, W."Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR". International Journal of Molecular Medicine 55, no. 3 (2025): 44. https://doi.org/10.3892/ijmm.2025.5485
Copy and paste a formatted citation
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Spandidos Publications style
Huang Y, Chien P, Wang W, Hsu L, Huang Y and Chang W: Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR. Int J Mol Med 55: 44, 2025.
APA
Huang, Y., Chien, P., Wang, W., Hsu, L., Huang, Y., & Chang, W. (2025). Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR. International Journal of Molecular Medicine, 55, 44. https://doi.org/10.3892/ijmm.2025.5485
MLA
Huang, Y., Chien, P., Wang, W., Hsu, L., Huang, Y., Chang, W."Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR". International Journal of Molecular Medicine 55.3 (2025): 44.
Chicago
Huang, Y., Chien, P., Wang, W., Hsu, L., Huang, Y., Chang, W."Tribbles pseudokinase 3 drives cancer stemness in oral squamous cell carcinoma cells by supporting the expression levels of SOX2 and EGFR". International Journal of Molecular Medicine 55, no. 3 (2025): 44. https://doi.org/10.3892/ijmm.2025.5485
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