Par-4 drives trafficking and activation of Fas and FasL to induce prostate cancer cell apoptosis and tumor regression

Mala Chakraborty, Shirley Guofang Qiu, Vivek M. Rangnekar, Krishna Murthi Vasudevan

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Prostate cancer cells are generally resistant to apoptosis by conventional therapy. During a search for molecules that may overcome prostate cancer cell survival mechanisms, we identified the prostate apoptosis response-4 (Par-4) gene. Par-4 induced apoptosis of selective prostate cancer cells PC-3, DU-145, and TSU-Pr and caused tumor regression by inhibition of NF-κB activity and cell membrane trafficking of Fas and FasL that leads to the activation of the Fas-Fas-associated death domain-caspase-8 pro-death pathway. Neither Fas pathway activation alone nor inhibition of NF-κB activity with IκB-super repressor was sufficient to induce apoptosis of prostate cancer cells. Coregulation of these two pathways was essential and sufficient for Par-4 to induce apoptosis. On the other hand, prostate cancer cells LNCaP or normal prostatic epithelial cells that were resistant to apoptosis by Par-4 did not show Fas or FasL trafficking. These findings identify a mechanism of apoptosis by Par-4 and suggest that Par-4 may have therapeutic potential.

Original languageEnglish
Pages (from-to)7255-7263
Number of pages9
JournalCancer Research
Volume61
Issue number19
StatePublished - Oct 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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