Cancer-Selective Apoptosis by Tumor Suppressor Par-4

  • Nikhil Hebbar
  • Tripti Shrestha-Bhattarai
  • Vivek M. RangnekarEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 818)


Tumor suppressor genes play an important role in preventing neoplastic transformation and maintaining normal tissue homeostasis. Par-4 is one such tumor suppressor which is unique in its ability to selectively induce apoptosis in cancer cells while leaving the normal cells unaffected. The cancer cell specific activity of Par-4 is elicited through intracellular as well as extracellular mechanisms. Intracellularly Par-4 acts through the inhibition of pro-survival pathways and activation of Fas mediated apoptosis whereas extracellular (secreted Par-4) acts by binding to cell surface GRP78 leading to activation of the extrinsic apoptotic pathway. Many studies have highlighted the importance of Par-4 not only in preventing cancer development/recurrence but also as a promising anticancer therapeutic agent.


Par-4/PAWR Apoptosis Tumor suppressor protein Extracellular systemic effects Prostate cancer 



This study was supported by KLCR grant and NIH/NCI grant CA060872 (to VMR). The authors thank the past and present members of the Rangnekar Laboratory and collaborators who contributed to the work described in this review article.


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Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Nikhil Hebbar
    • 1
  • Tripti Shrestha-Bhattarai
    • 1
  • Vivek M. Rangnekar
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Graduate Center for ToxicologyUniversity of KentuckyLexingtonUSA
  2. 2.Departments of Radiation MedicineUniversity of KentuckyLexingtonUSA
  3. 3.Microbiology, Immunology and Molecular GeneticsUniversity of KentuckyLexingtonUSA
  4. 4.L. P. Markey Cancer CenterUniversity of KentuckyLexingtonUSA

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