NUMB does not impair growth and differentiation status of experimental gliomas

Euskirchen, Philipp; Skaftnesmo, Kai-Ove; Huszthy, Peter C.; Brekka, Narve; Bjerkvig, Rolf; Miletić, Hrvoje

doi:10.1016/j.yexcr.2011.09.002

Cited by 15 publications

(20 citation statements)

References 33 publications

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“…The reason for the reduction in the proliferation of U87 and U118 GB cells when MSI2 is knocked down is also unclear. Recently, it has been reported that elevating NUMB in U87 cells does not affect their proliferation [50]. Thus, further study will be needed to define the roles of MSI2 in brain tumor cells.…”

Section: Discussionmentioning

confidence: 99%

The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells

et al. 2013

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“…The production and titration of lentiviral vectors were performed as described previously [18]. For infection, spheroids were dissociated using the Neuronal dissociation kit (Miltenyi, Bergisch-Gladbach, Germany), plated in round-bottomed 96 wells with 3,000 cells/well in culture medium with 4 % methylcellulose, and infected with viral supernatants at an MOI of 5–30.…”

Section: Methodsmentioning

confidence: 99%

EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis

et al. 2013

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Angiogenesis is regarded as a hallmark of cancer progression and it has been postulated that solid tumor growth depends on angiogenesis. At present, however, it is clear that tumor cell invasion can occur without angiogenesis, a phenomenon that is particularly evident by the infiltrative growth of malignant brain tumors, such as glioblastomas (GBMs). In these tumors, amplification or overexpression of wild-type (wt) or truncated and constitutively activated epidermal growth factor receptor (EGFR) are regarded as important events in GBM development, where the complex downstream signaling events have been implicated in tumor cell invasion, angiogenesis and proliferation. Here, we show that amplification and in particular activation of wild-type EGFR represents an underlying mechanism for non-angiogenic, invasive tumor growth. Using a clinically relevant human GBM xenograft model, we show that tumor cells with EGFR gene amplification and activation diffusely infiltrate normal brain tissue independent of angiogenesis and that transient inhibition of EGFR activity by cetuximab inhibits the invasive tumor growth. Moreover, stable, long-term expression of a dominant-negative EGFR leads to a mesenchymal to epithelial-like transition and induction of angiogenic tumor growth. Analysis of human GBM biopsies confirmed that EGFR activation correlated with invasive/non-angiogenic tumor growth. In conclusion, our results indicate that activation of wild-type EGFR promotes invasion and glioblastoma development independent of angiogenesis, whereas loss of its activity results in angiogenic tumor growth.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-013-1101-1) contains supplementary material, which is available to authorized users.

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“…However, the role of Numb in tumorigenesis differs in other types of tumors. In experimental glioma, Numb overexpression does not exert a tumor suppressor function and does not impair cell proliferation in vitro or induce differentiation of neural or glial cells (18). Additionally, two newly-identified isoforms of Numb, Numb5 and Numb6, have been revealed to act as oncogenes (9).…”

Section: Introductionmentioning

confidence: 99%

Role of Numb expression and nuclear translocation in endometrial cancer

et al. 2015

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The cell fate determinant Numb orchestrates numerous cell physiological and pathological processes and previous evidence has indicated that Numb expression is associated with tumorigenesis. The present study investigated the potential role of Numb in endometrial cancer (EC). Numb expression was compared between the normal endometrium and EC tissue by immunohistochemistry, and the protein levels were assessed by western blotting and confocal microscopy in the human endometrial HEC-1B cancer cell line and normal epithelial cells. The intracellular localization of Numb in HEC-1B cells was examined by immunofluorescence. Numb was found to be expressed at higher levels in endometrial cancer compared with the normal endometrium. Although Numb localizes to the cytoplasm and plasma membrane in the normal epithelium, the present study found that Numb accumulated in the nucleus of HEC-1B cells. The present data reveals the upregulation of Numb expression in EC tissues and indicates that Numb plays a role in the occurrence of EC, which may be mediated by its translocation into the nucleus. The role of Numb in cancer development requires additional investigation.

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NUMB does not impair growth and differentiation status of experimental gliomas

Cited by 15 publications

References 33 publications

The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells

The SOX2-Interactome in Brain Cancer Cells Identifies the Requirement of MSI2 and USP9X for the Growth of Brain Tumor Cells

EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis

Role of Numb expression and nuclear translocation in endometrial cancer

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