SPOP and cancer: a systematic review.

The initiation and progression of cancer is dependent on the acquisition of mutations in oncogenes or tumor suppressor genes that ultimately leads to the dysregulation of key regulatory pathways. Though these mutations often occur in direct regulators of such pathways, some may confer tumorigenic potential by indirectly targeting several pathways congruently thereby exerting pleiotropic effects. In recent years, the tumor suppressor gene Speckle Type POZ Protein (SPOP) has gained a lot of attention as it has been found to be altered in a variety of different cancers. SPOP appears to exert pleiotropic tumorigenic effects as multiple different regulatory pathways become dysregulated upon SPOP alterations. SPOP has been identified as an E3 ubiquitin ligase substrate binding subunit of the proteasome complex. Since protein degradation is critical in regulating proper cellular function it is not surprising that the proteasome pathway is often found to be disrupted in cancer. Many studies have now indicated that mutations or changes in the expression of SPOP are one of several underlying reasons of proteasome pathway disruption in different cancers. Ultimately, either SPOP downregulation or mutation promotes stabilization of direct SPOP targets which subsequently promotes cancer through the dysregulation of key regulatory pathways. In this review, we will discuss the current literature on cancer-specific SPOP alterations as well the SPOP targets that are stabilized, and the pathways that are dysregulated, as a result.