Abstract 5433: β-Tubulin inhibitors reduce GLUT1 membrane trafficking to attenuate tumorigenesis in glioblastoma subtypes
Bibliographic record
Abstract
Abstract Glioblastoma is an aggressive, high-grade tumor with poor prognosis due to lack of sound therapeutic options. Mesenchymal subtype GBMs are particularly difficult to treat because they tend to proliferate in the sub ventricular zone, an area that breeds stem-like neural cells and proves nearly impossible to access for surgical resection. They also contribute to creating a hypoxic microenvironment and switch to glycolytic metabolism in what is known as the Warburg Effect. Here, we hypothesize that strategically inhibiting the glucose transporter, GLUT1, through cytoskeletal components that traffic it to the cell membrane may reverse the Warburg Effect, attenuating further tumorigenesis and decreasing the stemness of such cells. Datamining studies and immunoblot analysis conducted on human glioblastoma patient specimens (hGBM) demonstrated that GLUT1 is highly upregulated. Limiting dilution assay conducted using GLUT1 inhibitors- fasentin and 2-Deoxy-D-glucose reduced the proliferation in mesenchymal cancer stem cell (CSC) subtype in in vitro culture. Simultaneously, mass spectrometric analysis revealed significant association between GLUT1 and β-tubulin 4 (TUBB4) in mesenchymal subtyped cells. This association was further confirmed by large-sample datamining and in immunoprecipitation studies from hGBM specimens, suggesting that TUBB4 may be a viable target in deterring the trafficking of upregulated GLUT1 to the membrane. Collectively, these studies confirm that GLUT1 is associated with TUBB4, and that targeting TUBB4 via siRNA or colchicine derivatives could prove effective in reversing the Warburg Effect in GBM cells and ultimately improve patient outcomes. Citation Format: Collin M. Labak, Maheedhara R. Guda, Swapna Asuthkar, Neha Jain, Yining Lu, Ian Purvis, Jack Tuszynski, Ichiro Nakano, Andrew J. Tsung, Kiran K. Velpula. β-Tubulin inhibitors reduce GLUT1 membrane trafficking to attenuate tumorigenesis in glioblastoma subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5433. doi:10.1158/1538-7445.AM2017-5433
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".