Cancer-selective apoptosis by tumor suppressor par-4

Adv Exp Med Biol. 2014:818:155-66. doi: 10.1007/978-1-4471-6458-6_7.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis*
  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Protein Binding
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Endoplasmic Reticulum Chaperone BiP
  • FAS protein, human
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Tumor Suppressor Proteins
  • fas Receptor
  • prostate apoptosis response-4 protein