Functional diversity of PFKFB3 splice variants in glioblastomas
Heydasch, U.; Kessler, R.; Warnke, J.-P.; Eschrich, K.; Scholz, N.; Bigl, M.
Show abstract
Tumor cells tend to metabolize glucose through aerobic glycolysis instead of oxidative phosphorylation in mitochondria. One of the rate limiting enzymes of glycolysis is 6-phosphofructo-1-kinase, which is allosterically activated by fructose 2,6-bisphosphate which in turn is produced by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2 or PFKFB). Mounting evidence suggests that cancerous tissues overexpress the PFKFB isoenzyme, PFKFB3, being causing enhanced proliferation of cancer cells. Initially, six PFKFB3 splice variants with different C-termini have been documented in humans. More recently, additional splice variants with varying N-termini were discovered the functions of which are to be uncovered. Glioblastoma is one of the deadliest forms of brain tumors. Up to now, the role of PFKFB3 splice variants in the progression and prognosis of glioblastomas is only partially understood. In this study, we first re-categorized the PFKFB3 splice variant repertoire to simplify the denomination. We investigated the impact of increased and decreased levels of PFKFB3-4 (former UBI2K4) and PFKFB3-5 (former variant 5) on the viability and proliferation rate of glioblastoma U87 and HEK-293 cells. The simultaneous knock-down of PFKFB3-4 and PFKFB3-5 led to a decrease in viability and proliferation of U87 and HEK-293 cells as well as a reduction in HEK-293 cell colony formation. Overexpression of PFKFB3-4 but not PFKFB3-5 resulted in increased cell viability and proliferation. This finding contrasts with the common notion that overexpression of PFKFB3 enhances tumor growth, but instead suggests splice variant-specific effects of PFKFB3, apparently with opposing effects on cell behaviour. Strikingly, in line with this result, we found that in human IDH-wildtype glioblastomas, the PFKFB3-4 to PFKFB3-5 ratio was significantly shifted towards PFKFB3-4 when compared to control brain samples. Our findings indicate that the expression level of distinct PFKFB3 splice variants impinges on tumorigenic properties of glioblastomas and that splice pattern may be of important diagnostic value for glioblastoma.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting Nuclear Factor I/B (NFIB) 94%
- Tau-tubulin kinase 1 and amyloid-β peptide induce phosphorylation of collapsin response mediator protein-2 and enhance neurite degeneration in Alzheimer disease mouse models 93%
- EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma 92%
Similar papers in this journal
- NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells. 94%
- Promyelocytic Leukemia Protein regulates Angiogenesis and Epithelial-Mesenchymal Transition to limit metastasis in MDA-MB-231 breast cancer cells. 94%
- RASSF1A independence and early Galectin-1 upregulation in PIK3CA induced hepatocarcinogenesis: new therapeutic venues 93%
Similar papers in this journal
- APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression 93%
- Oncoprotein 18 is necessary for malignant cell proliferation in bladder cancer cells and serves as a G3-specific non-invasive diagnostic marker candidate in urinary RNA 93%
- Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimers disease reveal intraneuronal Abeta42 accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ flux dysregulation: Therapeutic implications 92%
Similar papers in this journal
- The large GTPase Guanylate-Binding Protein-1 (GBP-1) promotes mitochondrial fission in glioblastoma. 93%
- Pro-apoptotic and anti-invasive properties underscore the tumor suppressing impact of myoglobin on subset of human breast cancer cells 92%
- Individual expression of hepatitis A virus 3C protease induces ferroptosis in human cells in vitro 92%
Similar papers in this journal
- Modest changes in Spi1 dosage reveal the potential for altered microglial function as seen in Alzheimers disease 93%
- Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response. 93%
- Analysing the effect of full-length and C-terminally truncated progranulin on proliferation, colony formation, and migration in HepG2 and U87 cells 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.