A gain of function paradox: Targeted therapy for glioblastoma associated with abnormal NHE9 expression.

A gain of function paradox: Targeted therapy for glioblastoma associated with abnormal NHE9 expression. J Cell Mol Med. 2019 Sep 18;: Authors: Pall AE, Juratli L, Guntur D, Bandyopadhyay K, Kondapalli KC Abstract Glioblastoma (GBM) is the most frequent and inevitably lethal primary brain cancer in adults. It is recognized that the overexpression of the endosomal Na+ /H+ exchanger NHE9 is a potent driver of GBM progression. Patients with NHE9 overexpression have a threefold lower median survival relative to GBM patients with normal NHE9 expression, using available treatment options. New treatment strategies tailored for this GBM subset are much needed. According to the prevailing model, NHE9 overexpression leads to an increase in plasma membrane density of epidermal growth factor receptors (EGFRs) which consequently enhances GBM cell proliferation and migration. However, this increase is not specific to EGFRs. In fact, the hallmark of NHE9 overexpression is a pan-specific increase in plasma membrane receptors. Paradoxically, we report that this gain of function in NHE9 can be exploited to effectively target GBM cells for destruction. When exposed to gold nanoparticles, NHE9 overexpressing GBM cells accumulated drastically high amounts of gold via receptor-mediated endocytosis, relative to control. Irradiation of these cells with near-infrared light led to apoptotic tumour cell death. A major limitation for delivering therapeutics to G...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research