文章基本信息

标题：Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner
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作者：Hee Jung Yang ; Jin Zhang ; Wensheng Yan 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：43
页码：11500-11505
DOI：10.1073/pnas.1711814114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：WT p53 is critical for tumor suppression, whereas mutant p53 promotes tumor progression. Nerve injury-induced protein 1 (Ninj1) is a target of p53 and forms a feedback loop with p53 by repressing p53 mRNA translation. Here, we show that loss of Ninj1 increased mutant p53 expression and, subsequently, enhanced cell growth and migration in cells carrying a mutant p53. In contrast, loss of Ninj1 inhibited cell growth and migration in cells carrying a WT p53. To explore the biological significance of Ninj1, we generated a cohort of Ninj1 -deficient mice and found that Ninj1 ^+/− mice were prone to systemic inflammation and insulitis, but not to spontaneous tumors. We also found that loss of Ninj1 altered the tumor susceptibility in both mutant p53 and p53 -null background. Specifically, in a mutant p53(R270H) background, Ninj1 deficiency shortened the lifespan, altered the tumor spectrum, and increased tumor burden, likely via enhanced expression of mutant p53. In a p53 -null background, Ninj1 deficiency significantly increased the incidence of T-lymphoblastic lymphoma. Taken together, our data suggest that depending on p53 genetic status, Ninj1 has two opposing functions in tumorigenesis and that the Ninj1–p53 loop may be targeted to manage inflammatory diseases and cancer.
关键词：Ninjurin 1 ; mutant p53 ; p53 ; inflammation ; cell adhesion