Researchers from Washington University School of Medicine, St.Louis have discovered that even for brain cancer stem cells exist fatal weakness. Two important protein, SOX2 and CDC20, play key role in remaining the characters in brain cancer stem cells. This study was published in Cell Reports.

Glioblastoma, the most common malignant primary tumor in adults, remain a challenging disease with a poor prognosis. Increasing appreciation of the cancer cell heterogeneity within glioblastomas has focused attention on a subpopulation of cells called tumor-initiating cells or glioblastoma stem-like cells (GSCs).

The anaphase-promoting complex (APC) E3 ubiquitin ligase functions with co-activator CDC20 to drive mitosis. CDC20-APC has been viewed as a potential strategic target in several human cancers. CDC20 mRNA is elevated in glioblastoma compared to low-grade gliomas, and CDC20 immunoreactivity in gliomas correlates with pathological grade, but little is known about the biological roles of CDC20-APC in glioblastoma.

In this study, researchers report CDC20-APC is required for GSC invasiveness and self-renewal in a manner distinct from its role in cell-cycle control. They identify pluripotency-related transcription factor SOX2 as a CDC20-interacting protein and show CDC20-APC operates through SOX2 to regulate human GSC in invasion and self-renewal. Finally, they demonstrate that CDC20-APC is essential for GSC tumorigenicity in orthotopic xenografts and that CDC20 expression has prognostic value in a subset of glioblastoma patients.

These results highlight a critical role for CDC20-APC in the maintenance of human GSC function, and they suggest that targeting this pathway in glioblastoma may disrupt the GSC state.