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| Status |
Public on Feb 14, 2019 |
| Title |
The ALK downregulated target gene HBP1 and repressor of MYCN activity as synergistic target for combined PI3K/HDAC inhibition [microarray] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
ALK mutations occur in 10% of primary neuroblastoma and represent a major target for precision treatment. In combination with MYCN amplification, ALK mutations infer an ultra-high-risk phenotype with very poor prognosis. To anticipate to future precision drugging, a deeper understanding of the molecular consequences of constitutive ALK signaling and its relationship to MYCN activity in this aggressive pediatric tumor, will be essential to understand treatment responses and failure as well as to ensure improved design of drugging combinations. We show that mutant ALK downregulates the HMG-box transcription factor 1 (HBP1) through the PI3K-AKT-FOXO3a signaling axis. Interestingly, we also demonstrate that HBP1 is under control of MYCN, through negative regulation of the miR-17~92 cluster. Moreover, modulation of HBP1 in neuroblastoma negatively affect MYCN activity, including alleviating MYCN/PRC2 controlled gene repression. Combined targeting of PI3K and MYCN signaling induced strong synergistic blocking of tumor growth, thus offering potential for targeted therapeutic interventions.
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| Overall design |
Gene expression was measured in NGP HBP1 neuroblastoma cells upon lentiviral transduction with an HBP1 overexpression construct. This was performed for 2 biological replicates.
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| Contributor(s) |
Claeys S, De Preter K, Speleman F |
| Citation(s) |
30538293 |
| Submission date |
Feb 13, 2017 |
| Last update date |
Jun 04, 2019 |
| Contact name |
Shana Claeys |
| Organization name |
Center for Medical Genetics Ghent
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| Street address |
De Pintelaan 185
|
| City |
Ghent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE95193 |
The ALK downregulated target gene HBP1 and repressor of MYCN activity as synergistic target for combined PI3K/HDAC inhibition |
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| Relations |
| BioProject |
PRJNA374498 |
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