In the last several years, multiple lines of evidence have suggested that the
COP9 signalosome (CSN) plays a significant role in the regulation of multiple
cancers and could be an attractive target for therapeutic intervention. First, the CSN plays a key role in the regulation of
Cullin-containing
ubiquitin E3
ligases that are central mediators of a variety of cellular functions essential during
cancer progression. Second, several studies suggest that the individual subunits of the CSN, particularly CSN5, might regulate oncogenic and
tumor suppressive functions independently of, or coordinately with, the CSN holocomplex. Thus, deregulation of CSN subunit function can have a dramatic effect on diverse cellular functions, including the maintenance of
DNA fidelity, cell cycle control, DNA repair, angiogenesis, and microenvironmental homeostasis that are critical for
tumor development. Additionally, clinical studies have suggested that the expression or localization of some CSN subunits correlate to
disease progression or clinical outcome in a variety of
tumor types. Although the study of CSN function in relation to
tumor progression is in its infancy, this review will address current studies in relation to
cancer initiation, progression, and potential for therapeutic intervention.