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Subjugation of TGFβ Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining

Overview of attention for article published in Clinical Cancer Research, December 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

Mentioned by

twitter
7 tweeters
patent
1 patent
wikipedia
2 Wikipedia pages

Citations

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53 Dimensions

Readers on

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54 Mendeley
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Title
Subjugation of TGFβ Signaling by Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma Shifts DNA Repair from Homologous Recombination to Alternative End Joining
Published in
Clinical Cancer Research, December 2018
DOI 10.1158/1078-0432.ccr-18-1346
Pubmed ID
Authors

Qi Liu, Lin Ma, Trevor Jones, Luis Palomero, Miquel Angel Pujana, Haydeliz Martinez-Ruiz, Patrick K. Ha, John Murnane, Isabel Cuartas, Joan Seoane, Michael Baumann, Annett Linge, Mary Helen Barcellos-Hoff

Abstract

Following cytotoxic therapy, 70% of patients with human papillomavirus (HPV) positive oropharyngeal head and neck squamous cell carcinoma (HNSCC) are alive at 5 years compared to 30% of those with similar HPV-negative cancer, which is thought to be due to dysregulation of DNA repair. Loss of transforming growth factor β (TGFβ) signaling is a poorly studied consequence of HPV that could contribute to this phenotype. Human HNSCC cell lines (n=9), patient-derived xenografts (n=9), tissue microarray (n=194), TCGA expression data and primary tumor specimens (n=10) were used to define the relationship between TGFβ competency, response to DNA damage, and type of DNA repair. Analysis of HNSCC specimens in situ and in vitro showed that HPV associates with loss of TGFβ signaling that increases the response to radiation or cisplatin. TGFβ suppressed miR-182 that inhibited both BRCA1, necessary for homologous recombination repair, and FOXO3, which is required for ATM kinase activity. TGFβ signaling blockade by either HPV or inhibitors released this control, compromised HRR and increased response to PARP inhibition. Antagonizing miR-182 rescued the homologous recombination deficit in HPV+ cells. Loss of TGFβ signaling unexpectedly increased error-prone, alternative end-joining repair. HPV-positive HNSCC cells are unresponsive to TGFβ. Abrogated TGFβ signaling compromises homologous recombination and shifts reliance on alt-EJ repair that provides a mechanistic basis for sensitivity to PARP inhibitors. The effect of HPV in HNSCC provides critical validation of TGFβ's role in DNA repair proficiency and further raises the translational potential of TGFβ inhibitors in cancer therapy.

Twitter Demographics

The data shown below were collected from the profiles of 7 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 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 54 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 19%
Researcher 9 17%
Other 6 11%
Student > Bachelor 5 9%
Student > Doctoral Student 3 6%
Other 6 11%
Unknown 15 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 28%
Medicine and Dentistry 12 22%
Agricultural and Biological Sciences 4 7%
Immunology and Microbiology 3 6%
Computer Science 2 4%
Other 1 2%
Unknown 17 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 15 May 2022.
All research outputs
#2,636,512
of 21,340,902 outputs
Outputs from Clinical Cancer Research
#2,268
of 12,105 outputs
Outputs of similar age
#55,605
of 299,134 outputs
Outputs of similar age from Clinical Cancer Research
#42
of 189 outputs
Altmetric has tracked 21,340,902 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,105 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has done well, scoring higher than 81% 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 299,134 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 81% of its contemporaries.
We're also able to compare this research output to 189 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.