Paracrine apoptotic effect of p53 mediated by tumor suppressor Par-4

Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53-/- or Par-4-/- mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 induced Par-4 secretion by suppressing the expression of its binding partner, UACA, which sequesters Par-4. Thus, normal cells can be empowered by p53 activation to induce Par-4 secretion for the inhibition of therapy-resistant tumors.

Original languageEnglish
Pages (from-to)271-277
Number of pages7
JournalCell Reports
Issue number2
StatePublished - 2014

Bibliographical note

Funding Information:
This study was supported by KLCR and NIH/NCI grant CA060872 (to V.M.R.).

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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