Inactivation of CK1α in multiple myeloma empowers drug cytotoxicity by affecting AKT and β-catenin survival signaling pathways.

ABSTRACT: Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells. We demonstrated that CK1α inactivation, while toxic for myeloma cells, is dispensable for the survival of healthy B lymphocytes and stromal cells. Disruption of CK1α function in myeloma cells resulted in decreased Mdm2, increased p53 and p21 and reduced expression of β-catenin and AKT. These effects were mediated partially by p53 and caspase activity. Finally,

SUBMITTER: Manni S 

PROVIDER: S-EPMC5362429 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature