Izumi H, Kaneko Y

Asymmetric cell division (ACD) is a physiological process during development and tissue homeostasis. ACD produces two unequal daughter cells; one has stem/progenitor cell activity and the other has potential for differentiation. Recent studies showed that misregulation of the balance between self-renewal and differentiation by ACD may lead to tumorigenesis in ...

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Drosophila neuroblasts. However, it is still largely unknown whether human cancer stem-like cells (CSC) exhibit ACD or not. Here, using human neuroblastoma cells as an ACD model, we found that MYCN accumulates at spindle poles by GSK-3β phosphorylation during mitosis. In parallel, the ACD-related ubiquitin ligase Trim32 was recruited to spindle poles by CDK1/cyclin B-mediated phosphorylation. Trim32 interacted with MYCN at spindle poles during mitosis, facilitating proteasomal degradation of MYCN at spindle poles and inducing ACD. Trim32 also suppressed sphere formation of neuroblastoma-initiating cells, suggesting that the mechanisms of ACD produce differentiated neuroblastoma cells that will eventually die. Thus, Trim32 is a positive regulator of ACD that acts against MYCN and should be considered a tumor suppressor candidate. Our findings offer novel insights into the mechanisms of asymmetric cell divions and clarify its contributions to human tumorigenesis.

Date: Aug. 06, 2014

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