The p75 neurotrophin receptor is a central regulator of glioma invasion.

Angela L.M. Johnston, Xueqing Lun, Jennifer J. Rahn, Abdelhamid Liacini, Limei Wang, Mark G. Hamilton, Ian F Parney, Barbara L. Hempstead, Stephen M. Robbins, Peter A. Forsyth, Donna L. Senger

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The invasive nature of cancers in general, and malignant gliomas in particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using a novel invasive glioma mouse model established by serial in vivo selection, we identified the p75 neurotrophin receptor (p75(NTR)) as a critical regulator of glioma invasion. Through a series of functional, biochemical, and clinical studies, we found that p75(NTR) dramatically enhanced migration and invasion of genetically distinct glioma and frequently exhibited robust expression in highly invasive glioblastoma patient specimens. Moreover, we found that p75(NTR)-mediated invasion was neurotrophin dependent, resulting in the activation of downstream pathways and producing striking cytoskeletal changes of the invading cells. These results provide the first evidence for p75(NTR) as a major contributor to the highly invasive nature of malignant gliomas and identify a novel therapeutic target.

Original languageEnglish (US)
JournalPLoS Biology
Volume5
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Nerve Growth Factor Receptor
neurotrophins
Glioma
receptors
Nerve Growth Factors
therapeutics
neoplasms
Tumors
rendering
Glioblastoma
Chemical activation
clinical trials
Neoplasms
animal models
Therapeutics
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Johnston, A. L. M., Lun, X., Rahn, J. J., Liacini, A., Wang, L., Hamilton, M. G., ... Senger, D. L. (2007). The p75 neurotrophin receptor is a central regulator of glioma invasion. PLoS Biology, 5(8). https://doi.org/10.1371/journal.pbio.0050212

The p75 neurotrophin receptor is a central regulator of glioma invasion. / Johnston, Angela L.M.; Lun, Xueqing; Rahn, Jennifer J.; Liacini, Abdelhamid; Wang, Limei; Hamilton, Mark G.; Parney, Ian F; Hempstead, Barbara L.; Robbins, Stephen M.; Forsyth, Peter A.; Senger, Donna L.

In: PLoS Biology, Vol. 5, No. 8, 08.2007.

Research output: Contribution to journalArticle

Johnston, ALM, Lun, X, Rahn, JJ, Liacini, A, Wang, L, Hamilton, MG, Parney, IF, Hempstead, BL, Robbins, SM, Forsyth, PA & Senger, DL 2007, 'The p75 neurotrophin receptor is a central regulator of glioma invasion.', PLoS Biology, vol. 5, no. 8. https://doi.org/10.1371/journal.pbio.0050212
Johnston ALM, Lun X, Rahn JJ, Liacini A, Wang L, Hamilton MG et al. The p75 neurotrophin receptor is a central regulator of glioma invasion. PLoS Biology. 2007 Aug;5(8). https://doi.org/10.1371/journal.pbio.0050212
Johnston, Angela L.M. ; Lun, Xueqing ; Rahn, Jennifer J. ; Liacini, Abdelhamid ; Wang, Limei ; Hamilton, Mark G. ; Parney, Ian F ; Hempstead, Barbara L. ; Robbins, Stephen M. ; Forsyth, Peter A. ; Senger, Donna L. / The p75 neurotrophin receptor is a central regulator of glioma invasion. In: PLoS Biology. 2007 ; Vol. 5, No. 8.
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