Cancer-Selective Apoptosis by Tumor Suppressor Par-4
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.
KeywordsPar-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.