DDX3 loss by p53 inactivation promotes tumor malignancy via the MDM2/Slug/E-cadherin pathway and poor patient outcome in non-small-cell lung cancer
作者： D-W Wu , M-C Lee , J Wang , C-Y Chen , Y-W Cheng
DOI: 10.1038/ONC.2013.107
关键词:
摘要: P53 inactivation by p53 mutation and E6 oncoprotein has a crucial role in human carcinogenesis. DDX3 been shown to be target of p53. In this study, we hypothesized that loss may promote tumor malignancy poor patients' outcome. Mechanically, knockdown overexpression was observed A549 lung cancer cells. Conversely, expression markedly elevated wild-type (WT) ectopic p53-null H1299 cells, E6-knockdown TL-1 SiHa cervical Interestingly, promotes soft-agar growth invasive capability; however, both capabilities were suppressed overexpression. We next expected might result Slug-suppressed E-cadherin via decreased MDM2-mediated Slug degradation. As expected, MDM2 transcription is SP1 binding activity the promoter. Consequently, reduction because loss, Slug. Consistent observations correlation with MDM2, seen tumors from patients. addition, patients low-DDX3 had poorer survival relapse than high-DDX3 tumors. conclusion, suggest MDM2/Slug/E-cadherin pathway patient
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