The Role of Neurotrophin Signaling in Gliomagenesis: A Focus on the p75 Neurotrophin Receptor (p75 NTR /CD271).
| Autor: | Alshehri MM; Arnie Charbonneau Cancer Centre, University of Calgary, Calgary, AB, Canada., Robbins SM; Arnie Charbonneau Cancer Centre, University of Calgary, Calgary, AB, Canada., Senger DL; Arnie Charbonneau Cancer Centre, University of Calgary, Calgary, AB, Canada. Electronic address: senger@ucalgary.ca. |
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| Jazyk: | angličtina |
| Zdroj: | Vitamins and hormones [Vitam Horm] 2017; Vol. 104, pp. 367-404. Date of Electronic Publication: 2017 Jan 04. |
| DOI: | 10.1016/bs.vh.2016.11.001 |
| Abstrakt: | The p75 neurotrophin receptor (p75 NTR , a.k.a. CD271), a transmembrane glycoprotein and a member of the tumor necrosis family (TNF) of receptors, was originally identified as a nerve growth factor receptor in the mid-1980s. While p75 NTR is recognized to have important roles during neural development, its presence in both neural and nonneural tissues clearly supports the potential to mediate a broad range of functions depending on cellular context. Using an unbiased in vivo selection paradigm for genes underlying the invasive behavior of glioma, a critical characteristic that contributes to poor clinical outcome for glioma patients, we identified p75 NTR as a central regulator of glioma invasion. Herein we review the expanding role that p75 NTR plays in glioma progression with an emphasis on how p75 NTR may contribute to the treatment refractory nature of glioma. Based on the observation that p75 NTR is expressed and functional in two critical glioma disease reservoirs, namely, the highly infiltrative cells that evade surgical resection, and the radiation- and chemotherapy-resistant brain tumor-initiating cells (also referred to as brain tumor stem cells), we propose that p75 NTR and its myriad of downstream signaling effectors represent rationale therapeutic targets for this devastating disease. Lastly, we provide the provocative hypothesis that, in addition to the well-documented cell autonomous signaling functions, the neurotrophins, and their respective receptors, contribute in a cell nonautonomous manner to drive the complex cellular and molecular composition of the brain tumor microenvironment, an environment that fuels tumorigenesis. (© 2017 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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