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X Demographics
Mendeley readers
Attention Score in Context
| Title |
SMAD4 Loss Is Associated with Cetuximab Resistance and Induction of MAPK/JNK Activation in Head and Neck Cancer Cells
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|---|---|
| Published in |
Clinical Cancer Research, August 2017
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| DOI | 10.1158/1078-0432.ccr-16-1686 |
| Pubmed ID | |
| Authors |
Hiroyuki Ozawa, Ruchira S. Ranaweera, Evgeny Izumchenko, Eugene Makarev, Alex Zhavoronkov, Elana J. Fertig, Jason D. Howard, Ana Markovic, Atul Bedi, Rajani Ravi, Jimena Perez, Quynh-Thu Le, Christina S. Kong, Richard C. Jordan, Hao Wang, Hyunseok Kang, Harry Quon, David Sidransky, Christine H. Chung |
| Abstract |
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. Experimental Design: SMAD4 expression was assessed by immunohistochemistry in 130 newly diagnosed and 43 recurrent HNSCC patients. Correlative statistical analysis with clinicopathological data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels. The role of SMAD4 was investigated by shRNA knockdown and gene reconstitution of HPV-negative HNSCC cell lines in vitro and in vivoResults: Our analysis revealed that SMAD4 loss was associated with an aggressive, HPV-negative, cetuximab-resistant phenotype. We found a signature of pro-survival and anti-apoptotic pathways that were commonly dysregulated in SMAD4-low cases derived from TCGA-HNSCC dataset and an independent oral cavity squamous cell carcinoma (OSCC) cohort obtained from GEO. We show that SMAD4 depletion in a HNSCC cell line induces cetuximab resistance and results in worse survival in an orthotopic mouse model in vivo We implicate JNK and MAPK activation as mediators of cetuximab resistance and provide the foundation for the concomitant EGFR and JNK/MAPK inhibition as a potential strategy for overcoming cetuximab resistance in HNSCCs with SMAD4 loss. Conclusions: Our study demonstrates that loss of SMAD4 expression is a signature characterizing the cetuximab-resistant phenotype and suggests that SMAD4 expression may be a determinant of sensitivity/resistance to EGFR/MAPK or EGFR/JNK inhibition in HPV-negative HNSCC tumors. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 62 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 18% |
| Researcher | 7 | 11% |
| Student > Bachelor | 6 | 10% |
| Student > Postgraduate | 6 | 10% |
| Professor > Associate Professor | 4 | 6% |
| Other | 11 | 18% |
| Unknown | 17 | 27% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 18 | 29% |
| Biochemistry, Genetics and Molecular Biology | 8 | 13% |
| Agricultural and Biological Sciences | 5 | 8% |
| Immunology and Microbiology | 3 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
| Other | 5 | 8% |
| Unknown | 21 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 15. 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 01 December 2022.
All research outputs
#2,095,002
of 23,230,825 outputs
Outputs from Clinical Cancer Research
#1,710
of 12,691 outputs
Outputs of similar age
#42,008
of 316,764 outputs
Outputs of similar age from Clinical Cancer Research
#40
of 244 outputs
Altmetric has tracked 23,230,825 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,691 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.0. This one has done well, scoring higher than 86% of its peers.
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 316,764 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 244 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.