ヤマウチ　アキラ   Akira Yamauchi   山内　明    所属   川崎医科大学  医学部 基礎医学　生化学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	DKK3/CKAP4 axis is associated with advanced stage and poorer prognosis in oral cancer.
掲載誌名	正式名：Oral Diseases 略　 称：Oral Dis ISSNコード：16010825
掲載区分	国外
出版社	John Wiley & Sons, Inc.
著者・共著者	Naoki Katase,Kodai Kudo,Kazuhiro Ogawa,Yae Sakamoto,Shin-ichiro Nishimatsu,Akira Yamauchi,Shuichi Fujita
発行年月	2022/06/16
概要	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