Proteasome dysregulation in human cancer: implications for clinical therapies

Cancer cells show heightened dependency on the proteasome for their survival, growth, and spread. Proteasome dysregulation is therefore commonly selected in favor of the development of many types of cancer. The vast abnormalities in a cancer cell, on top of the complexity of the proteasome itself, have enabled a plethora of mechanisms gearing the proteasome to the oncogenic process. Here, we use selected examples to highlight some general mechanisms underlying proteasome dysregulation in cancer, including copy number variations, transcriptional control, epigenetic regulation, and post-translational modifications. Research in this field has greatly advanced our understanding of proteasome regulation and will shed new light on proteasome-based combination therapies for cancer treatment.