Accumulation of ubiquitin-conjugated cytokeratin fragments in tumor cells.

Ubiquitin regulates cell functions by modifying various proteins, and cytokeratin (CK) is one of the targets of ubiquitilation. Accumulation of modified CK in various cancers has been demonstrated, and the modified CK increases the aggressiveness of the cancer by disrupting the cytoplasmic CK network and allows them to move freely. The phenotype of the cancer cells may be altered in such a way as to facilitate invasion and metastasis. Modified CK also deregulates mechanisms of mitosis and apoptosis, and leads to immortalization. Therapeutic targeting of ubiquitin or ubiquitilated proteins may reduce the malignant potential of cancer cells.