NHERF-1 Protein Complexes, Cancer Progression and Therapeutic Targeting


Researchers at TGen have patented a method of detecting invasive glioblastoma in a subject and sensitizing the subject to a therapeutic treatment that targets non-migrating glioblastoma cells. Specifically, our researchers have discovered that Na+/H+ exchanger regulatory factor (NHERF-1) is over-expressed in invasive GBM cells and have confirmed its role as a regulator of glioma migration and dispersion.


NHERF-1 is as a multi-functional adaptor protein that recruits cytoplasmic signaling proteins and membrane receptors/transporters into functional complexes. Our studies found that NHERF-1 expression was restricted to cancer cells (glioma) and the vascular endothelium, with minimal to no detection in adjacent normal tissue (brain).  Additionally, depletion of NHERF-1 arrested migration and dispersion of glioma cell lines and caused an increase in cell-cell adhesion.  Furthermore, when NHERF-1 expression was reduced, glioma cells became sensitized to Temozolomide treatment resulting in increased apoptosis. 


These results provide the first evidence for NHERF-1 as a participant in the phenotype of highly malignant cancers including glioblastoma, breast cancer, schwannoma, and hepatocellular carcinoma.  For this reason, NHERF-1 can be used as a diagnostic and prognostic marker, and may even serve as a target for anti-cancer therapeutics.  Ongoing translational steps include immunohistochemistry for NHERF-1 across a cancer tissue microarray, testing for consequences of disrupting NHERF-1 protein complexes relative to cancer invasion and cell survival. 


Link to Issued US Patent 8,962,581


Link to Issued US Patent 9,587,239


Patent Information:
For Information, Contact:
Katie Bray
Intellectual Property Counsel
The Translational Genomics Research Institute
Michael Berens
Kerri Kislin
Cancer & Cell Biology