Document Type

Journal Article

Publication Date

1-1-2015

Journal

Nature Communications

Volume

6

Inclusive Pages

5909

DOI

10.1038/ncomms6909.

Keywords

Antigens, CD24--metabolism; Proto-Oncogene Proteins c-mdm2--metabolism; Tumor Suppressor Protein p14ARF--metabolism; Tumor Suppressor Protein p53--metabolism

Abstract

CD24 is overexpressed in nearly 70% human cancers, whereas TP53 is the most frequently mutated tumour-suppressor gene that functions in a context-dependent manner. Here we show that both targeted mutation and short hairpin RNA (shRNA) silencing of CD24 retard the growth, progression and metastasis of prostate cancer. CD24 competitively inhibits ARF binding to NPM, resulting in decreased ARF, increase MDM2 and decrease levels of p53 and the p53 target p21/CDKN1A. CD24 silencing prevents functional inactivation of p53 by both somatic mutation and viral oncogenes, including the SV40 large T antigen and human papilloma virus 16 E6-antigen. In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels. These data provide a general mechanism for functional inactivation of ARF and reveal an important cellular context for genetic and viral inactivation of TP53.

Comments

Reproduced with permission of Nature Publishing Group. Nature Communications.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

Peer Reviewed

1

Open Access

1

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