| Title |
Phenotypic heterogeneity of disseminated tumour cells is preset by primary tumour hypoxic microenvironments
|
|---|---|
| Published in |
Nature Cell Biology, January 2017
|
| DOI | 10.1038/ncb3465 |
| Pubmed ID | |
| Authors |
Georg Fluegen, Alvaro Avivar-Valderas, Yarong Wang, Michael R. Padgen, James K. Williams, Ana Rita Nobre, Veronica Calvo, Julie F. Cheung, Jose Javier Bravo-Cordero, David Entenberg, James Castracane, Vladislav Verkhusha, Patricia J. Keely, John Condeelis, Julio A. Aguirre-Ghiso |
| Abstract |
Hypoxia is a poor-prognosis microenvironmental hallmark of solid tumours, but it is unclear how it influences the fate of disseminated tumour cells (DTCs) in target organs. Here we report that hypoxic HNSCC and breast primary tumour microenvironments displayed upregulation of key dormancy (NR2F1, DEC2, p27) and hypoxia (GLUT1, HIF1α) genes. Analysis of solitary DTCs in PDX and transgenic mice revealed that post-hypoxic DTCs were frequently NR2F1(hi)/DEC2(hi)/p27(hi)/TGFβ2(hi) and dormant. NR2F1 and HIF1α were required for p27 induction in post-hypoxic dormant DTCs, but these DTCs did not display GLUT1(hi) expression. Post-hypoxic DTCs evaded chemotherapy and, unlike ER(-) breast cancer cells, post-hypoxic ER(+) breast cancer cells were more prone to enter NR2F1-dependent dormancy. We propose that primary tumour hypoxic microenvironments give rise to a subpopulation of dormant DTCs that evade therapy. These post-hypoxic dormant DTCs may be the source of disease relapse and poor prognosis associated with hypoxia. |
X Demographics
The data shown below were collected from the profiles of 81 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 | 19 | 23% |
| United Kingdom | 5 | 6% |
| Spain | 3 | 4% |
| Canada | 3 | 4% |
| Italy | 2 | 2% |
| Australia | 2 | 2% |
| Denmark | 1 | 1% |
| Poland | 1 | 1% |
| Philippines | 1 | 1% |
| Other | 13 | 16% |
| Unknown | 31 | 38% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 40 | 49% |
| Scientists | 37 | 46% |
| Science communicators (journalists, bloggers, editors) | 3 | 4% |
| Practitioners (doctors, other healthcare professionals) | 1 | 1% |
Mendeley readers
The data shown below were compiled from readership statistics for 334 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | <1% |
| Finland | 1 | <1% |
| Japan | 1 | <1% |
| Unknown | 329 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 92 | 28% |
| Researcher | 68 | 20% |
| Student > Master | 33 | 10% |
| Student > Bachelor | 23 | 7% |
| Student > Doctoral Student | 18 | 5% |
| Other | 52 | 16% |
| Unknown | 48 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 113 | 34% |
| Agricultural and Biological Sciences | 57 | 17% |
| Medicine and Dentistry | 42 | 13% |
| Engineering | 13 | 4% |
| Immunology and Microbiology | 12 | 4% |
| Other | 31 | 9% |
| Unknown | 66 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 112. 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 03 October 2019.
All research outputs
#382,908
of 25,738,558 outputs
Outputs from Nature Cell Biology
#180
of 4,166 outputs
Outputs of similar age
#8,194
of 424,755 outputs
Outputs of similar age from Nature Cell Biology
#4
of 35 outputs
Altmetric has tracked 25,738,558 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,166 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.5. This one has done particularly well, scoring higher than 95% of its peers.
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