|
Status |
Public on Jul 03, 2018 |
Title |
Targeting oncogenic β-catenin/CBP activity for the treatment of head and neck squamous cell carcinoma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
Head and neck squamous cell carcinoma (HNSCC) presents primarily as oral squamous cell carcinoma (OSCC), an aggressive malignancy characterized by heterogeneity, locoregional metastases and resistance to existing treatments. Although a number of molecular alterations associated with OSCC have been identified, they have had limited impact on clinical management. A frequent feature of OSCC is the inappropriate activation of nuclear β-catenin. Here, we provide a comprehensive characterization of the effects of blocking the interaction between nuclear β-catenin and the cAMP-responsive element binding (CREB)-binding protein (CBP) using the small molecule inhibitor ICG-001. We demonstrate that ICG-001 inhibits cell proliferation and aggressive OSCC cell phenotypes in cellular, zebrafish and murine models, and that its inhibition-associated transcriptional signature tracks with advanced tumor grade and poor survival in human patients. Our results suggest that targeting the β-catenin/CBP interaction in the nucleus represents a new and effective therapy for OSCC.
|
|
|
Overall design |
Microarray gene expression profiling pertaining to ICG-001 or DMSO (control) treatment in HSC-3 and CAL27 cells, and siCTNNB1 or scrambled siRNA control in HSC-3 cells ; n=3 per treatment group, per cell line).
Note: the preprocessed data were generated from two normalizations: 1) samples GSM2522361-GSM2522372, and 2) samples GSM2522373-GSM2522378, plus six other arrays that are not included in this Series. The preprocessed data for samples GSM2522373-GSM2522378 therefore cannot be reproduced entirely from this Series alone.
|
|
|
Contributor(s) |
Kartha V, Kukuruzinska M |
Citation(s) |
30029671 |
Submission date |
Mar 06, 2017 |
Last update date |
Jun 25, 2019 |
Contact name |
Boston University Microarray and Sequencing Resource |
E-mail(s) |
msrdata@bu.edu
|
Organization name |
Boston University
|
Department |
Microarray and Sequencing Resource
|
Street address |
72 East Concord Street, E631
|
City |
Boston |
State/province |
MA |
ZIP/Postal code |
02118 |
Country |
USA |
|
|
Platforms (1) |
GPL17930 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [HuGene20stv1_Hs_ENTREZG_17.0.0] |
|
Samples (18)
|
|
Relations |
BioProject |
PRJNA378165 |