The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces senescence or quiescence of prostate, breast and liver cancer cells via transcriptional activation of p53.

Tumor suppressive actions of the autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here, we showed that sPDZD2 induced senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. Furthermore, sPDZD2 sensitized mutant p53-positive DU145 cells and wild-type p53-positive MCF-7 cells to apoptosis induction through genotoxic stress imposed by sub-lethal concentration of hydrogen peroxide. Together, our findings suggest a potential autocrine pathway of p53 activation by transcriptional regulation, and a new approach to reactivate p53 for cancer therapy.