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P4HA2 contributes to head and neck squamous cell carcinoma progression and EMT through PI3K/AKT signaling pathway

Yan-Ling Wu1, Wan Liu2, Tingting Zhao2

  • 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518116, Guangdong, China.

Medical Oncology (Northwood, London, England)
|May 22, 2024
PubMed

Insights

Overexpression of P4HA2 significantly promotes head and neck squamous cell carcinoma (HNSCC) progression, enhancing cell proliferation, migration, and invasion via the PI3K/AKT pathway. P4HA2 silencing reverses these effects, indicating its role as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Head and neck squamous cell carcinoma (HNSCC) presents a dismal prognosis in advanced stages.
  • Understanding the molecular mechanisms driving HNSCC progression is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the expression pattern and functional role of P4HA2 in HNSCC.
  • To elucidate the underlying molecular mechanisms, including the involvement of the PI3K/AKT signaling pathway and epithelial-mesenchymal transition (EMT).

Main Methods:

  • Integrated bioinformatics analyses were performed to assess P4HA2 expression and prognostic value.
  • In vitro experiments (colony formation, CCK-8, flow cytometry, wound healing, Transwell assays) were conducted on the CAL-27 HNSCC cell line.
  • Western blotting was utilized to analyze EMT and PI3K/AKT pathway markers; specific inhibitors were used to confirm pathway involvement.

Main Results:

  • P4HA2 expression was significantly upregulated in HNSCC tissues and correlated with tumor aggressiveness and poor patient prognosis.
  • Overexpression of P4HA2 promoted cell proliferation, migration, invasion, and EMT, while reducing apoptosis in HNSCC cells.
  • P4HA2 overexpression enhanced PI3K/AKT pathway activation, and inhibition of this pathway counteracted the pro-tumorigenic effects of P4HA2.

Conclusions:

  • P4HA2 acts as a significant driver of HNSCC progression and metastasis.
  • The pro-tumorigenic effects of P4HA2 are mediated through the activation of the PI3K/AKT signaling pathway, leading to enhanced EMT.
  • P4HA2 represents a potential therapeutic target for HNSCC treatment.
Keywords:
EMTHead and neck squamous cell carcinomaP4HA2PI3K/AKT pathwayPrognostic marker

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