Medulloblastomas and
glioblastomas, the most common
primary brain tumors in children and adults, respectively, are extremely difficult to treat. Efforts to identify novel
proteins essential for the growth of these
tumors may help to further our understanding of the biology of these
tumors, as well as, identify targets for future
therapies. The recent identification of multiple
transcription factor-centric
protein interaction landscapes in embryonic stem cells has identified numerous understudied
proteins that are essential for the self-renewal of these stem cells. To identify novel
proteins essential for the fate of
brain tumor cells, we examined the protein interaction network of the
transcription factor, SOX2, in
medulloblastoma cells. For this purpose, Multidimensional
Protein Identification Technology (MudPIT) identified >280 SOX2-associated
proteins in the
medulloblastoma cell line DAOY. To begin to understand the roles of SOX2-associated
proteins in
brain cancer, we focused on two SOX2-associated
proteins, Musashi 2 (MSI2) and
Ubiquitin Specific Protease 9x (USP9X). Recent studies have implicated MSI2, a putative
RNA binding protein, and USP9X, a
deubiquitinating enzyme, in several
cancers, but not
brain tumors. We demonstrate that knockdown of MSI2 significantly reduces the growth of DAOY cells as well as U87 and U118
glioblastoma cells. We also demonstrate that the knockdown of USP9X in DAOY, U87 and U118
brain tumor cells strongly reduces their growth. Together, our studies identify a large set of SOX2-associated
proteins in DAOY
medulloblastoma cells and identify two
proteins, MSI2 and USP9X, that warrant further investigation to determine whether they are potential therapeutic targets for
brain cancer.