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Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer

Overview of attention for article published in Genome Medicine, July 2018
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  • Good Attention Score compared to outputs of the same age (66th percentile)

Mentioned by

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3 tweeters
wikipedia
1 Wikipedia page

Citations

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27 Dimensions

Readers on

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53 Mendeley
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Title
Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer
Published in
Genome Medicine, July 2018
DOI 10.1186/s13073-018-0569-7
Pubmed ID
Authors

Vinay K. Kartha, Khalid A. Alamoud, Khikmet Sadykov, Bach-Cuc Nguyen, Fabrice Laroche, Hui Feng, Jina Lee, Sara I. Pai, Xaralabos Varelas, Ann Marie Egloff, Jennifer E. Snyder-Cappione, Anna C. Belkina, Manish V. Bais, Stefano Monti, Maria A. Kukuruzinska

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of this disease. To date, few targeted therapies are available for HNSCC, and only a small fraction of patients have benefited from these treatments. A frequent feature of HNSCC is the inappropriate activation of β-catenin that has been implicated in cell survival and in the maintenance and expansion of stem cell-like populations, thought to be the underlying cause of tumor recurrence and resistance to treatment. However, the therapeutic value of targeting β-catenin activity in HNSCC has not been explored. We utilized a combination of computational and experimental profiling approaches to examine the effects of blocking the interaction between β-catenin and cAMP-responsive element binding (CREB)-binding protein (CBP) using the small molecule inhibitor ICG-001. We generated and annotated in vitro treatment gene expression signatures of HNSCC cells, derived from human oral squamous cell carcinomas (OSCCs), using microarrays. We validated the anti-tumorigenic activity of ICG-001 in vivo using SCC-derived tumor xenografts in murine models, as well as embryonic zebrafish-based screens of sorted stem cell-like subpopulations. Additionally, ICG-001-inhibition signatures were overlaid with RNA-sequencing data from The Cancer Genome Atlas (TCGA) for human OSCCs to evaluate its association with tumor progression and prognosis. ICG-001 inhibited HNSCC cell proliferation and tumor growth in cellular and murine models, respectively, while promoting intercellular adhesion and loss of invasive phenotypes. Furthermore, ICG-001 preferentially targeted the ability of subpopulations of stem-like cells to establish metastatic tumors in zebrafish. Significantly, interrogation of the ICG-001 inhibition-associated gene expression signature in the TCGA OSCC human cohort indicated that the targeted β-catenin/CBP transcriptional activity tracked with tumor status, advanced tumor grade, and poor overall patient survival. Collectively, our results identify β-catenin/CBP interaction as a novel target for anti-HNSCC therapy and provide evidence that derivatives of ICG-001 with enhanced inhibitory activity may serve as an effective strategy to interfere with aggressive features of HNSCC.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 53 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 23%
Student > Bachelor 7 13%
Student > Master 5 9%
Student > Doctoral Student 4 8%
Researcher 4 8%
Other 12 23%
Unknown 9 17%
Readers by discipline Count As %
Medicine and Dentistry 14 26%
Biochemistry, Genetics and Molecular Biology 12 23%
Agricultural and Biological Sciences 7 13%
Immunology and Microbiology 4 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 3 6%
Unknown 11 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 December 2021.
All research outputs
#5,693,249
of 21,322,016 outputs
Outputs from Genome Medicine
#957
of 1,354 outputs
Outputs of similar age
#97,796
of 298,915 outputs
Outputs of similar age from Genome Medicine
#1
of 1 outputs
Altmetric has tracked 21,322,016 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 1,354 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.9. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 298,915 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them