The p75 neurotrophin receptor is central regulator of Glioma invasion (Plos Biol, 2007, 5:1723-1737)

報告日期: 2008/05/23
報告時間: 17:10/18:00
報告學生: 鄧志娟
講評老師: 辛致煒

The p75 Neurotrophin Receptor Is a Central Regulator of Glioma Invasion

PLoS biology, 2007. 5:1723-1737


Speaker: 鄧志娟

Commentator: 辛致煒 教授

Time: 2008/5/230, 15:10-16:00

Place: Room 602



    Human malignant gliomas are highly invasive tumors. This highly invasive nature with an extremely poor prognosis owing to recurrence of the tumor outside the margin of therapeutic resection. For owing the highly invasive nature these glioma cells activate a number of coordinate cellular programs that involve the regulation of many molecules, including adhesion molecules, extracellular matrix constituents, proteases, cytoskeleton components, and signaling molecules. Identification of key regulatory proteins of glioma invasion is extremely important clinically because this will be used to provide therapeutically relevant targets to prevent malignant glioma recurrence at the invasive margin of gliomas. p75NTR is a transmembrane glycoprotein and a member of the tumor necrosis factor (TNF) superfamily that was originally isolated as a nerve growth factor (NGF) receptor. In neurons, p75NTR is coexpressed with a second group of neurotrophin receptors, the tropomysin receptor kinases (Trks). It has become increasingly clear that the dogma in neuroscience that Trks mediate neuronal survival and p75NTR causes neuronal cell death. Rather, there is a growing appreciation that p75NTR, like other members in the TNF superfamily, mediates a very broad range of cellular functions, depending on the cell context and the repertoire of co-receptors that exist. In this study, the auther using a novel invasive glioma mouse model established by serial in vivo selection, identified the p75 neurotrophin receptor (p75NTR) as a critical regulator of glioma invasion. And founding that p75NTR-mediated invasion was neurotrophin dependent, resulting in the activation of downstream pathways and producing striking cytoskeletal changes of the invading cells. Depending on this finding, authers suggested therapies that target p75NTR, p75NTR downstream effectors, or their ligands may not only be beneficial for malignant glioma, but may target other metastatic diseases.         


1.   Joy AM, Beaudry CE, Tran NL, Ponce FA, Holz DR, et al. (2003) Migrating glioma cells activate the PI3-K pathway and display decreased susceptibility to apoptosis. J Cell Sci 116: 4409–4417.

2.   Roux PP, Barker PA (2002) Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol 67: 203–233.