Malignant gliomas are diffuse and highly invasive tumors arising from glial cells in the central nervous system. Persons with malignant gliomas have a poor prognosis, with an average patient survival rate of less than 1 year. The p75 neurotrophin receptor (p75NTR) is one crucial regulator of glioma invasiveness. Here, Wang et al. investigate the mechanism underlying neurotrophin-mediated tumor invasiveness. Glioma cells expressing either wild-type or cleavage-resistant p75NTR were implanted into mouse brains and, in contrast to typical glioma infiltration, cleavage-resistant p75NTR cells formed well-defined tumors. Furthermore, inhibition of the cleavage enzyme γ-secretase prevented tumor cell invasion and prolonged survival in the mice implanted with wild-type p75NTR cells. In combination with in vitro experiments using patient tumor samples, these studies demonstrate that proteolytic processing of p75NTR is a major mechanism underlying glioma invasiveness and that targeting γ-secretase might be key in preventing the spread of these tumors.
Cancer: protein processing aids the spread of malignant gliomas
Cancer: protein processing aids the spread of malignant gliomas. Dis Model Mech 7 January 2009; 2 (1-2): 2–3. doi:
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