Akira Yamauchi
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Biochemistry,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title DKK3/CKAP4 axis is associated with advanced stage and poorer prognosis in oral cancer.
Journal Formal name：Oral Diseases
Abbreviation：Oral Dis
ISSN code：16010825
Domestic / ForeginForegin
Publisher John Wiley & Sons, Inc.
Author and coauthor Naoki Katase,Kodai Kudo,Kazuhiro Ogawa,Yae Sakamoto,Shin-ichiro Nishimatsu,Akira Yamauchi,Shuichi Fujita
Publication date 2022/06/16
Summary Objective
We previously reported that dickkopf WNT signaling inhibitor 3 (DKK3) would modulate malignant potential of oral squamous cell carcinoma (OSCC) via activating Akt. Recently, cytoskeleton associated protein 4 (CKAP4) functions as receptor of DKK3, which activates Akt in esophageal squamous cell carcinoma, but its expression and function in OSCC were unclear.

Methods
We studied DKK3 and CKAP4 protein expression in OSCC tissue and investigated the correlation between protein expression and clinical data. We also investigated whether antibodies (Ab) for DKK3 or CKAP4 could suppress malignant potential of the cancer cells.

Results
DKK3/CKAP4 protein expression was observed in majority of OSCC cases and was associated with significantly higher T-stage and TNM stage. Multivariate analysis revealed that DKK3 and CKAP4 were independent prognostic biomarkers for overall survival (OS) and disease-free survival (DFS), respectively. Survival analyses revealed that DKK3-positive cases and CKAP4-positive cases showed significantly shorter OS and DFS, respectively, and that DKK3/CKAP4 double-negative cases showed significantly favorable prognosis. Both anti-DKK3Ab and anti-CKAP4Ab could suppress cancer cell proliferation, migration, and invasion.

Conclusion
DKK3/CKAP4 axis is thought to be important in OSCC, and it would be a promising therapeutic target.
DOI 10.1111/odi.14277
PMID 35708905