Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner

Hee Jung Yang, Jin Zhang, Wensheng Yan, Seong Jun Cho, Christopher Lucchesi, Mingyi Chen, Eric C Huang, Ariane Scoumanne, Weici Zhang, Xinbin Chen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11500-11505
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number43
DOIs
StatePublished - Oct 24 2017

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Carcinogenesis
Wounds and Injuries
Proteins
Protein Deficiency
Neoplasms
Cell Movement
Protein Biosynthesis
Growth
Tumor Burden
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Inflammation
Incidence

Keywords

  • Cell adhesion
  • Inflammation
  • Mutant p53
  • Ninjurin 1
  • P53

ASJC Scopus subject areas

  • General

Cite this

Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner. / Yang, Hee Jung; Zhang, Jin; Yan, Wensheng; Cho, Seong Jun; Lucchesi, Christopher; Chen, Mingyi; Huang, Eric C; Scoumanne, Ariane; Zhang, Weici; Chen, Xinbin.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 43, 24.10.2017, p. 11500-11505.

Research output: Contribution to journalArticle

Yang, Hee Jung ; Zhang, Jin ; Yan, Wensheng ; Cho, Seong Jun ; Lucchesi, Christopher ; Chen, Mingyi ; Huang, Eric C ; Scoumanne, Ariane ; Zhang, Weici ; Chen, Xinbin. / Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 43. pp. 11500-11505.
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