The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells

作者：Mi, L.; Zhu, F.; Yang, X.; Lu, J.; Zheng, Y.; Zhao, Q.; Wen, X.; Lu, A.; Wang, M.^*; Zheng, M.^*; Ji, J.; Sun, J.^*

来源：Oncogene, 2017, 36(30): 4323-4335.

DOI：10.1038/onc.2017.74

• EPITHELIAL-MESENCHYMAL TRANSITION
• RNA-POLYMERASE-II
• PROSTATE-CANCER
• PROTEASOMAL DEGRADATION
• INDUCED UBIQUITINATION
• ELEVATED EXPRESSION
• LUNG ADENOCARCINOMA
• SIGNALING PATHWAYS
• GENE-EXPRESSION
• DOWN-REGULATION

N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer.

• 出版日期2017-7-27
• 单位北京大学; 上海交通大学; 上海市闵行区中心医院