| Title |
Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance
|
|---|---|
| Published in |
Proceedings of the National Academy of Sciences of the United States of America, December 2017
|
| DOI | 10.1073/pnas.1712064115 |
| Pubmed ID | |
| Authors |
Yapeng Su, Wei Wei, Lidia Robert, Min Xue, Jennifer Tsoi, Angel Garcia-Diaz, Blanca Homet Moreno, Jungwoo Kim, Rachel H Ng, Jihoon W Lee, Richard C Koya, Begonya Comin-Anduix, Thomas G Graeber, Antoni Ribas, James R Heath |
| Abstract |
Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lead to therapy resistance and escape from immune control before establishing acquired resistance genetically. We used genome-wide transcriptomics and single-cell phenotyping to explore the response kinetics to BRAF inhibition for a panel of patient-derived BRAFV600 -mutant melanoma cell lines. A subset of plastic cell lines, which followed a trajectory covering multiple known cell state transitions, provided models for more detailed biophysical investigations. Markov modeling revealed that the cell state transitions were reversible and mediated by both Lamarckian induction and nongenetic Darwinian selection of drug-tolerant states. Single-cell functional proteomics revealed activation of certain signaling networks shortly after BRAF inhibition, and before the appearance of drug-resistant phenotypes. Drug targeting those networks, in combination with BRAF inhibition, halted the adaptive transition and led to prolonged growth inhibition in multiple patient-derived cell lines. |
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 | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 243 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 243 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 65 | 27% |
| Researcher | 48 | 20% |
| Student > Bachelor | 19 | 8% |
| Student > Postgraduate | 14 | 6% |
| Student > Master | 13 | 5% |
| Other | 25 | 10% |
| Unknown | 59 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 85 | 35% |
| Agricultural and Biological Sciences | 38 | 16% |
| Chemistry | 11 | 5% |
| Engineering | 11 | 5% |
| Medicine and Dentistry | 8 | 3% |
| Other | 23 | 9% |
| Unknown | 67 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 399. 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 September 2021.
All research outputs
#71,780
of 24,625,114 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#1,742
of 101,438 outputs
Outputs of similar age
#1,700
of 450,048 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#40
of 922 outputs
Altmetric has tracked 24,625,114 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one has done particularly well, scoring higher than 98% of its peers.
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We're also able to compare this research output to 922 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.