ARF and p53 Coordinate Tumor Suppression of an Oncogenic IFN-β-STAT1-ISG15 Signaling Axis

Jason T. Forys, Catherine E. Kuzmicki, Anthony J. Saporita, Crystal L. Winkeler, Leonard B. Maggi, Jason D. Weber

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The ARF and p53 tumor suppressors are thought to act in a linear pathway to prevent cellular transformation in response to various oncogenic signals. Here, we show that loss of p53 leads to an increase in ARF protein levels, which function to limit the proliferation and tumorigenicity of p53-deficient cells by inhibiting an IFN-β-STAT1-ISG15 signaling axis. Human triple-negative breast cancer (TNBC) tumor samples with coinactivation of p53 and ARF exhibit high expression of both STAT1 and ISG15, and TNBC cell lines are sensitive to STAT1 depletion. We propose that loss of p53 function and subsequent ARF induction creates a selective pressure toinactivate ARF and propose that tumors harboringcoinactivation of ARF and p53 would benefit from therapies targeted against STAT1 and ISG15 activation.

Original languageEnglish
Pages (from-to)514-526
Number of pages13
JournalCell Reports
Volume7
Issue number2
DOIs
StatePublished - Apr 24 2014

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