ANGPTL4 Induces TMZ Resistance of Glioblastoma by Promoting Cancer Stemness Enrichment via the EGFR/AKT/4E-BP1 Cascade
Abstract
:1. Introduction
2. Results
2.1. ANGPTL4 Induces TMZ Resistance in GBM Cells
2.2. ANGPTL4 Secretion by GBM Cells Increases GSC Enrichment
2.3. ANGPTL4 Regulates Stemness through the EGFR/AKT/4E-BP1 Cascade
2.4. Sp4 Increases ANGPTL4 Expression Leading to Stemness Development
2.5. High Expression of Sp4 and ANGPTL4 Correlate with a Poor Prognosis of GBM
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Human Specimens and Primary Glioblastoma Cells Pt#3
4.3. Chemicals
4.4. Transfection and Plasmids
4.5. Western Blotting
4.6. MTT Assay
4.7. Colony Formation
4.8. Phosphorylation Array
4.9. Reporter Assay
4.10. Chromatin Immunoprecipitation Coupled with Sequencing (ChIP-seq) and Data Analysis
4.11. Microarray Analysis
4.12. Databases
4.13. Immunohistochemistry (IHC)
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
4E-BP1 | Eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 |
AKAP12 | A-kinase anchoring protein 12 |
ANGPTL4 | Angiopoietin-like 4 protein |
CCN3 | Cellular communication network factor 3 |
CDK6 | Cyclin-dependent kinase 6 |
CEMIP | Cell migration-inducing hyaluronidase 1 |
ChIP-seq | Chromatin immunoprecipitation coupled with sequencing |
DMEM | Dulbecco’s Modified Eagle Medium |
DMSO | Dimethyl sulfoxide |
DOAJ | Directory of open access journals |
EGF | Epidermal growth factor |
EGFR | Epidermal growth factor receptor |
EGR1 | Early growth response protein 1 |
EGR2 | Early growth response protein 2 |
FGF | Fibroblast growth factor |
FGF1 | Fibroblast growth factor 1 |
ERK | Extracellular signal–regulated kinase |
GBM | Glioblastoma |
GSCs | Glioma stem-like cells |
IHC | Immunohistochemistry |
IPA | Ingenuity Pathway Analysis |
LD | linear dichroism |
LY96 | Lymphocyte antigen 96 |
MEME-ChIP | Motif analysis of large DNA datasets |
mTOR | Mammalian target of rapamycin |
NCBI | National Center for Biotechnology Information |
Poly-HEMA | Poly-2-hydroxyethyl methacrylate |
PI3K | Phosphoinositide 3-kinase |
rANGPTL4 | Human recombinant ANGPTL4 protein |
RTK | Receptor Tyrosine Kinase |
SNR | Signal-to-noise ratio |
Sp | Specificity protein |
SOX2 | SRY (sex determining region Y)-box 2 |
TLA | Three letter acronym |
TMZ | Temozolomide |
TYROBP | TYRO protein tyrosine kinase binding protein |
WNT5b | Wnt family member 5B |
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Tsai, Y.-T.; Wu, A.-C.; Yang, W.-B.; Kao, T.-J.; Chuang, J.-Y.; Chang, W.-C.; Hsu, T.-I. ANGPTL4 Induces TMZ Resistance of Glioblastoma by Promoting Cancer Stemness Enrichment via the EGFR/AKT/4E-BP1 Cascade. Int. J. Mol. Sci. 2019, 20, 5625. https://doi.org/10.3390/ijms20225625
Tsai Y-T, Wu A-C, Yang W-B, Kao T-J, Chuang J-Y, Chang W-C, Hsu T-I. ANGPTL4 Induces TMZ Resistance of Glioblastoma by Promoting Cancer Stemness Enrichment via the EGFR/AKT/4E-BP1 Cascade. International Journal of Molecular Sciences. 2019; 20(22):5625. https://doi.org/10.3390/ijms20225625
Chicago/Turabian StyleTsai, Yu-Ting, An-Chih Wu, Wen-Bin Yang, Tzu-Jen Kao, Jian-Ying Chuang, Wen-Chang Chang, and Tsung-I. Hsu. 2019. "ANGPTL4 Induces TMZ Resistance of Glioblastoma by Promoting Cancer Stemness Enrichment via the EGFR/AKT/4E-BP1 Cascade" International Journal of Molecular Sciences 20, no. 22: 5625. https://doi.org/10.3390/ijms20225625