PP2A deactivation is a common event in oral cancer and reactivation by FTY720 shows promising therapeutic potential

Bharath K Velmurugan1, Chien-Hung Lee2,3, Shang-Lun Chiang4,5

  • 1Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam.

Insights

Protein phosphatase 2A (PP2A) deactivation, marked by tyrosine-307 hyperphosphorylation, is common in oral cancer. Restoring PP2A with FTY720 may offer a therapeutic strategy for oral squamous cell carcinoma (OSCC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Protein phosphatase 2A (PP2A) acts as a tumor suppressor, frequently deactivated in various cancers.
  • The specific role and clinical significance of PP2A in oral squamous cell carcinoma (OSCC) are not well-established.

Purpose of the Study:

  • To investigate the deactivation mechanisms of PP2A in oral cancer.
  • To evaluate the clinical relevance of PP2A phosphorylation in OSCC patient outcomes.
  • To explore FTY720 as a potential therapeutic agent for OSCC.

Main Methods:

  • Assessed PP2A deactivation in oral cancer cells, focusing on tyrosine-307 (Y307) phosphorylation.
  • Treated cells with FTY720 to restore PP2A activity and monitored cell growth and downstream signaling (GSK-3β phosphorylation).
  • Analyzed PP2A phosphorylation levels in 262 OSCC tissue samples and correlated findings with clinical staging and patient survival.

Main Results:

  • PP2A deactivation via Y307 hyperphosphorylation is prevalent in oral cancer cells.
  • FTY720 treatment reactivated PP2A, inhibited cell growth, and reduced GSK-3β phosphorylation.
  • Elevated p-PP2A expression in tumors correlated with advanced N2/N3 stage and poorer overall survival, particularly in cases with lymph node metastasis.
  • High p-PP2A expression was a significant predictor of mortality density and reduced 10-year survival.

Conclusions:

  • PP2A deactivation is a frequent event in oral cancer, linked to poor prognosis.
  • Restoring PP2A function using FTY720 presents a potential therapeutic avenue for OSCC treatment.

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