title: Nrdp1 inhibits growth of colorectal cancer cells by nuclear retention of p27.
abstract: 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.
authors.affiliation: Department of Gastrointestinal Surgery, the First Affiliated Hospital, Liaoning Medical College, 5-2 People Road, Jinzhou, 121001, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Lu
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Mao
authors.forename: Zhitu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Sun
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D020893:Receptor, ErbB-3 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; C452580:RNF41 protein, human; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D020893:Receptor, ErbB-3; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases