The ultimate growth of a tumour depends on not only the rate of tumour cell proliferation, but also the rate of tumour cell death (apoptosis). Nur77 (also known as TR3 or NGFI-B), an orphan member of the
nuclear receptor superfamily, controls both survival and death of
cancer cells. A wealth of recent experimental data demonstrates that the Nur77 activities are regulated through its subcellular localisation. In the nucleus, Nur77 functions as an oncogenic survival factor, promoting
cancer cell growth. In contrast, it is a potent killer when migrating to mitochondria, where it binds to Bcl-2 and converts its survival phenotype, triggering
cytochrome c release and apoptosis. Agents, such
as 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-
naphthalene carboxylic acid (
AHPN/CD437), which induce Nur77 migration from the nucleus to mitochondria, effectively induce apoptosis of
cancer cells. Moreover, Nur77 translocation is highly controlled by
retinoid X receptor (RXR), suggesting a role of RXR
ligands in regulating the process. Thus, translocation of Nur77 from the nucleus to mitochondria represents a new paradigm in
cancer cell apoptosis, and targeting the Nur77 translocation by
AHPN/CD437 or RXR
ligands promises to effectively restrict
cancer cell growth by simultaneously promoting
cancer cell death and suppressing
cancer cell proliferation.