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The Clinical Significance of SPOP Upregulation and Nuclear Accumulation in Head and Neck Squamous Cell Carcinoma

Yin-Hwa Shih1, Nan-Chin Lin2, Yen-Wen Shen3

  • 1Department of Healthcare Administration, Asia University, Taichung 41354, Taiwan.

International Journal of Molecular Sciences
|March 14, 2026
PubMed

Insights

Speckle-type BTB/POZ protein (SPOP) is upregulated in head and neck squamous cell carcinoma (HNSCC). Increased nuclear SPOP indicates malignancy and progression, suggesting its potential as an HNSCC biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The role of Speckle-type BTB/POZ protein (SPOP), an E3 ubiquitin ligase adaptor, in head and neck squamous cell carcinoma (HNSCC) is not well understood.
  • While generally considered a tumor suppressor, SPOP's specific function in HNSCC warrants investigation.

Purpose of the Study:

  • To investigate SPOP expression levels and regulation by arecoline in HNSCC.
  • To evaluate the potential of SPOP as a diagnostic and progression biomarker for HNSCC.

Main Methods:

  • Quantification of SPOP mRNA and protein in HNSCC and normal oral epithelial cell lines using RT-qPCR and Western blot.
  • Assessment of arecoline's effect on SPOP expression in selected cell lines.
  • Analysis of SPOP mRNA in the TCGA HNSCC cohort and protein localization via immunohistochemistry on tissue microarrays.

Main Results:

  • SPOP mRNA was found to be higher in some HNSCC cell lines compared to normal cells.
  • Arecoline induced SPOP expression in normal oral epithelial cells but not in HNSCC cell lines.
  • TCGA data confirmed SPOP mRNA upregulation in HNSCC tumors, correlating with tumor grade.
  • Immunohistochemistry revealed SPOP upregulation in HNSCC tissues, particularly in palate and pharynx/hypopharynx.
  • A significant shift in nuclear SPOP-positive ratio from normal tissues (12.14%) to tumors (61.26%) was observed, differentiating grades and sites effectively.

Conclusions:

  • SPOP is upregulated in HNSCC and its expression can be induced by arecoline.
  • Enhanced nuclear localization of SPOP is indicative of malignancy and disease progression in HNSCC.
  • SPOP demonstrates potential as a valuable diagnostic and progression biomarker for HNSCC.
Keywords:
SPOParecolinebiomarkerhead and neck squamous cell carcinoma (HNSCC)nuclear localization

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