title: 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.
abstract: 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.
authors.affiliation: Department of Physiology, The University of Hong Kong, Laboratory Block, Faculty of Medicine Building, Hong Kong, China.
authors.forename: Chun Wai
authors.initials: CW
authors.lastname: Tam
authors.forename: Vincent Wing Sun
authors.initials: VW
authors.lastname: Liu
authors.forename: Wai Ying
authors.initials: WY
authors.lastname: Leung
authors.forename: Kwok-Ming
authors.initials: KM
authors.lastname: Yao
authors.forename: Stephen Yuen Wing
authors.initials: SY
authors.lastname: Shiu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D017209:Apoptosis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009363:Neoplasm Proteins / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D009363:Neoplasm Proteins; C423943:PDZD2 protein, human; D016159:Tumor Suppressor Protein p53