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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Epithelial-to-Mesenchymal Transition Antagonizes Response to Targeted Therapies in Lung Cancer by Suppressing BIM
|
|---|---|
| Published in |
Clinical Cancer Research, January 2018
|
| DOI | 10.1158/1078-0432.ccr-17-1577 |
| Pubmed ID | |
| Authors |
Kyung-A Song, Matthew J. Niederst, Timothy L. Lochmann, Aaron N. Hata, Hidenori Kitai, Jungoh Ham, Konstantinos V. Floros, Mark A. Hicks, Haichuan Hu, Hillary E. Mulvey, Yotam Drier, Daniel A.R. Heisey, Mark T. Hughes, Neha U. Patel, Elizabeth L. Lockerman, Angel Garcia, Shawn Gillepsie, Hannah L. Archibald, Maria Gomez-Caraballo, Tara J. Nulton, Brad E. Windle, Zofia Piotrowska, Sinem E. Sahingur, Shirley M. Taylor, Mikhail Dozmorov, Lecia V. Sequist, Bradley Bernstein, Hiromichi Ebi, Jeffrey A. Engelman, Anthony C. Faber |
| Abstract |
Epithelial-to-mesenchymal transition (EMT) confers resistance to a number of targeted therapies and chemotherapies. However, it has been unclear why EMT promotes resistance, thereby impairing progress to overcome it. We have developed several models of EMT-mediated resistance to EGFR inhibitors (EGFRi) in EGFR mutant lung cancers to evaluate a novel mechanism of EMT-mediated resistance. Results: We observed that mesenchymal EGFR mutant lung cancers are resistant to EGFRi-induced apoptosis via insufficient expression of BIM, preventing cell death despite potent suppression of oncogenic signaling following EGFRi treatment. Mechanistically, we observed that the EMT transcription factor ZEB1 inhibits BIM expression by binding directly to the BIM promoter and repressing transcription. De-repression of BIM expression by depletion of ZEB1 or treatment with the BH3 mimetic ABT-263 to enhance "free" cellular BIM levels both led to re-sensitization of mesenchymal EGFR mutant cancers to EGFR inhibitors. This relationship between EMT and loss of BIM is not restricted to EGFR mutant cancers as it was also observed in KRAS mutant lung cancers and large datasets including different cancer subtypes. Altogether, these data reveal a novel mechanistic link between EMT and resistance to lung cancer targeted therapies. |
X Demographics
The data shown below were collected from the profiles of 21 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 | 6 | 29% |
| Italy | 2 | 10% |
| France | 2 | 10% |
| Spain | 1 | 5% |
| Australia | 1 | 5% |
| Singapore | 1 | 5% |
| United Kingdom | 1 | 5% |
| Unknown | 7 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 11 | 52% |
| Practitioners (doctors, other healthcare professionals) | 5 | 24% |
| Scientists | 5 | 24% |
Mendeley readers
The data shown below were compiled from readership statistics for 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 73 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 14% |
| Student > Ph. D. Student | 9 | 12% |
| Other | 6 | 8% |
| Student > Postgraduate | 6 | 8% |
| Student > Master | 5 | 7% |
| Other | 14 | 19% |
| Unknown | 23 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 20 | 27% |
| Medicine and Dentistry | 13 | 18% |
| Agricultural and Biological Sciences | 5 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
| Unspecified | 3 | 4% |
| Other | 6 | 8% |
| Unknown | 23 | 32% |
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 30 March 2021.
All research outputs
#2,933,806
of 22,889,074 outputs
Outputs from Clinical Cancer Research
#2,567
of 12,605 outputs
Outputs of similar age
#68,655
of 441,192 outputs
Outputs of similar age from Clinical Cancer Research
#37
of 166 outputs
Altmetric has tracked 22,889,074 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 12,605 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.8. This one has done well, scoring higher than 79% 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 441,192 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 84% of its contemporaries.
We're also able to compare this research output to 166 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.