Mechanisms of apoptosis by the tumor suppressor Par-4

作者：Hebbar Nikhil; Wang Chi; Rangnekar Vivek M^*

来源：Journal of Cellular Physiology, 2012, 227(12): 3715-3721.

DOI：10.1002/jcp.24098

Par-4 is a pro-apoptotic, tumor suppressor protein that induces apoptosis selectively in cancer cells. Endoplasmic reticulum-stress and higher levels of protein kinase A in tumor cells confer the coveted feature of cancer selective response to extracellular and intracellular Par-4, respectively. Recent studies have shown that systemic Par-4 confers resistance to tumor growth in mice, and that tumor-resistance is transferable by bone-marrow transplantation. Moreover, recombinant Par-4 inhibits the growth of tumors in mice. As systemic Par-4 induces apoptosis via cell surface GRP78, strategies that promote GRP78 trafficking to the cell surface are expected sensitize cancer cells to circulating levels of Par-4. This review illustrates the domains and mechanisms by which Par-4 orchestrates the apoptotic process in both cell culture models and in physiological settings. J. Cell. Physiol. 227: 37153721, 2012.

• 出版日期2012-12