Neuroendocrine differentiation and the ubiquitin-proteasome system in cancer: Partners or enemies?

Neuroendocrine (NE) differentiation of cancer and deregulation of the ubiquitin-proteasome system (UPS) are two processes that have been independently linked to the development of aggressive and treatment-resistant tumors. Striking data suggest a plausible interconnection between these two mechanisms, based on indirect evidence of neuropeptide-induced effects on UPS, reversed by proteasome inhibition and deubiquitinase-like properties of NE markers. Deciphering the model of their exact interactions is one of the keys to targeting the NE malignant phenotype more effectively.