期刊
TUMOR BIOLOGY
卷 35, 期 9, 页码 8639-8643出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-014-2132-5
关键词
Neuregulin receptor degradation protein-1 (Nrdp1); ErbB3; Extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK); Phosphatidylinositol 3-kinase (PI3K); Proteinkinase B(Akt); Colorectal cancer
类别
资金
- First Affiliated Hospital, Liaoning Medical College, China
The molecular mechanism underlying the proliferation of colorectal cancer (CRC) cells is not completely understood. Here, we found that the level of neuregulin receptor degradation protein-1 (Nrdp1) E3 ubiquitin ligase was significantly decreased in CRC tissues, compared with the adjacent normal tissues from human patients. Knockdown of Nrdp1 enhanced the proliferation of CRC cells, while overexpression of Nrdp1 inhibited the proliferation of CRC cells. Further analysis showed that Nrdp1 may induce degradation of its target ErbB3 to inhibit activation of both ERK/MAPK and PI3K/Akt pathways in CRC cells, which seemed to affect cell proliferation via nuclear retention of a major cell-cycle inhibitor, p27. Taken together, these findings suggest that Nrdp1-mediated ErbB3 degradation suppresses cellular growth of CRC and that Nrdp1 loss in CRC may promote tumor progression, thus highlighting Nrdp1 as a novel target for CRC therapy.
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