Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, 400016, Chongqing, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, 610041, Chengdu, China.
Cell Death Dis. 2018 Aug 29;9(9):865. 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.
转移仍然是结直肠癌 (CRC) 临床治疗的一大障碍。我们之前的蛋白质组学分析发现 DJ-1 是 CRC 潜在的转移生物标志物。在这项研究中，我们发现 DJ-1 在 CRC 中上调。DJ-1 的水平与侵袭深度密切相关，并预测患者的预后。通过刺激 Wnt-β-catenin 信号，强制表达 DJ-1 可以在体外和体内增强 CRC 的增殖和转移。具体而言，DJ-1 诱导的 β-catenin 核易位刺激了 TCF 转录活性，分别促进了 CRC 细胞迁移和侵袭的 BMP4 表达以及 CRC 细胞增殖的 CCND1 表达。此外，DJ-1 诱导的 Wnt 信号激活依赖于 PLAGL2 的表达。总之，我们的研究表明，DJ-1 可以通过激活 PLAGL2-Wnt-BMP4 轴促进 CRC 转移，为 CRC 患者的术后辅助治疗提供了新的治疗机会。
