Cancers, Vol. 11, Pages 1308: GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets

Cancers, Vol. 11, Pages 1308: GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets Cancers doi: 10.3390/cancers11091308 Authors: Maheedhara R. Guda Collin M. Labak Sara Ibrahim Omar Swapna Asuthkar Subra Airala Jack Tuszynski Andrew J. Tsung Kiran K. Velpula Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor, portending a median 13-month survival even following gross total resection with adjuvant chemotherapy and radiotherapy. This prognosis necessitates improved therapies for the disease. A target of interest for novel chemotherapies is the Warburg Effect, which describes the tumor’s shift away from oxidative phosphorylation towards glycolysis. Here, we elucidate GLUT1 (Glucose transporter 1) and one of its associated binding partners, TUBB4 (Tubulin 4), as potentially druggable targets in GBM. Using data mining approach, we demonstrate that GLUT1 is overexpressed as a function of tumor grade in astrocytoma’s and that its overexpression is associated with poorer prognosis. Using both mass spectrometry performed on hGBM (human glioblastoma patient specimen) and in silico modeling, we show that GLUT1 interacts with TUBB4, and more accurately demonstrates GLUT1’s binding with fasentin. Proximity ligation assay (PLA) and immunoprecipitation studies confirm GLUT1 interaction with TUBB4. Treatment of GSC33 and GSC28 cells with TUBB4 inhibitor, CR-42-24, reduces the expression of GLUT1 ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research