DJ-1 promotes colorectal cancer progression through activating PLAGL2/Wnt/BMP4 axis

• Published in: Cell death & disease 2018-08, Vol.9 (9), p.865-12, Article 865
• Main Authors: Zhou, Jing, Liu, Hao, Zhang, Lian, Liu, Xin, Zhang, Chundong, Wang, Yitao, He, Qing, Zhang, Ying, Li, Yi, Chen, Quanmei, Zhang, Lu, Wang, Kui, Bu, Youquan, Lei, Yunlong
• Format: Article
• Language: English
• Subjects: 13; 38/91; 96/1; Antibodies; Biochemistry; Biomedical and Life Sciences; Cell adhesion & migration; Cell Biology; Cell Culture; Cell migration; Cell proliferation; Colorectal cancer; Colorectal carcinoma; Immunology; Life Sciences; Metastases; Metastasis; Nuclear transport; PARK7 protein; Patients; Proteomics; Transcription; Wnt protein; β-Catenin
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-0883-4

Metastasis remains a big barrier for the clinical treatment of colorectal cancer (CRC). Our previous proteomics analysis identified DJ-1 as a potential metastasis biomarker of CRC. In this study, we found that DJ-1 was upregulated in CRC. The levels of DJ-1 were closely correlated with the depths of invasion and predicted patient outcome. Enforced expression of DJ-1 could enhance CRC proliferation and metastasis in vitro and in vivo by stimulating Wnt-β-catenin signaling. Specifically, DJ-1-induced β-catenin nuclear translocation stimulated TCF transcription activity, which promoted BMP4 expression for CRC cell migration and invasion, and elevated CCND1 expression for CRC cell proliferation, respectively. Furthermore, DJ-1-induced Wnt signaling activation was dependent on PLAGL2 expression. In conclusion, our study demonstrates that DJ-1 can promote CRC metastasis by activating PLAGL2–Wnt–BMP4 axis, suggesting novel therapeutic opportunities for postoperative adjuvant therapy in CRC patients.