Brain Tumor Stem Cell Targeting Publications
Jennifer J. Rahna,b,d, Xueqing Luna,b,d, Selina K. Jorchc,e, Xiaoguang Haoa,b,d, Chitra Venugopalg, Parvez Vorag, Bo Young Ahna,b,d, Liane Babesa,b,d, Mana M. Alshehria,b,d,1, J. Gregory Cairncrossa,b,f, Sheila K. Singhg, Paul Kubesc,e, Donna L. Sengera,b,d,∗∗, Stephen M. Robbinsa,b,d,∗
a Arnie Charbonneau Cancer Institute, University of Calgary
b Clark H. Smith Brain Tumour Centre, University of Calgary
c Calvin, Phoebe & Joan Snyder Institute For Chronic Diseases, University of Calgary
d Departments of Oncology, University of Calgary
e Physiology and Pharmacology, University of Calgary
f Clinical Neurosciences, University of Calgary
g Department of Surgery, McMaster Children's Hospital, And McMaster Stem Cell and Cancer Research Institute, McMaster University
Despite extensive molecular characterization, human glioblastoma remains a fatal disease with ...
Gamma-secretase represents a therapeutic target for the treatment of invasive glioma mediated by the p75 neurotrophin receptor
The multifunctional signaling protein p75 neurotrophin receptor (p75(NTR)) is a central regulator and major contributor to the highly invasive nature of malignant gliomas. Here, we show that neurotrophin-dependent regulated intramembrane proteolysis (RIP) of p75(NTR) is required for p75(NTR)-mediated glioma invasion, and identify a previously unnamed process for targeted glioma therapy. Expression of cleavage-resistant chimeras of p75(NTR) or treatment of animals bearing p75(NTR)-positive intracranial tumors with clinically applicable gamma-secretase inhibitors resulted in dramatically decreased glioma invasion and prolonged survival. Importantly, proteolytic processing of p75(NTR) was observed in ...