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DKK3/CKAP4 axis is associated with advanced stage and poorer prognosis in oral cancer

Naoki Katase1, Kodai Kudo1,2, Kazuhiro Ogawa1,2

  • 1Department of Oral Pathology, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Oral Diseases
|June 16, 2022
PubMed
Abstract

Insights

The dickkopf WNT signaling inhibitor 3 (DKK3) and cytoskeleton associated protein 4 (CKAP4) axis promotes oral squamous cell carcinoma (OSCC) progression. Targeting this DKK3/CKAP4 pathway with antibodies offers a potential therapeutic strategy for OSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Dickkopf WNT signaling inhibitor 3 (DKK3) modulates oral squamous cell carcinoma (OSCC) malignancy by activating Akt.
  • Cytoskeleton associated protein 4 (CKAP4) acts as a DKK3 receptor, activating Akt in esophageal cancer, but its role in OSCC was unknown.

Purpose of the Study:

  • To investigate the expression and clinical significance of DKK3 and CKAP4 in OSCC.
  • To evaluate the potential of anti-DKK3 and anti-CKAP4 antibodies as therapeutic agents against OSCC.

Main Methods:

  • DKK3 and CKAP4 protein expression was analyzed in OSCC tissues.
  • Correlation between protein expression and clinical data was assessed.
  • The effect of anti-DKK3 and anti-CKAP4 antibodies on cancer cell behavior was examined.

Main Results:

  • DKK3 and CKAP4 were frequently expressed in OSCC and correlated with advanced T-stage and TNM stage.
  • DKK3 and CKAP4 served as independent prognostic biomarkers for overall survival and disease-free survival, respectively.
  • DKK3/CKAP4 double-negative status indicated a favorable prognosis, while antibodies against DKK3/CKAP4 inhibited cancer cell proliferation, migration, and invasion.

Conclusions:

  • The DKK3/CKAP4 axis plays a crucial role in OSCC progression.
  • Targeting the DKK3/CKAP4 pathway presents a promising therapeutic strategy for OSCC treatment.
Keywords:
CKAP4DKK3head and neck canceroral squamous cell carcinoma

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