| Title |
Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells
|
|---|---|
| Published in |
Oncotarget, August 2016
|
| DOI | 10.18632/oncotarget.11743 |
| Pubmed ID | |
| Authors |
Chuanzhao Zhang, Wanqing Iris Zhi, Haiquan Lu, Debangshu Samanta, Ivan Chen, Edward Gabrielson, Gregg L. Semenza |
| Abstract |
Exposure of breast cancer cells to hypoxia increases the percentage of breast cancer stem cells (BCSCs), which are required for tumor initiation and metastasis, and this response is dependent on the activity of hypoxia-inducible factors (HIFs). We previously reported that exposure of breast cancer cells to hypoxia induces the ALKBH5-mediated demethylation of N6-methyladenosine (m6A) in NANOG mRNA leading to increased expression of NANOG, which is a pluripotency factor that promotes BCSC specification. Here we report that exposure of breast cancer cells to hypoxia also induces ZNF217-dependent inhibition of m6A methylation of mRNAs encoding NANOG and KLF4, which is another pluripotency factor that mediates BCSC specification. Although hypoxia induced the BCSC phenotype in all breast-cancer cell lines analyzed, it did so through variable induction of pluripotency factors and ALKBH5 or ZNF217. However, in every breast cancer line, the hypoxic induction of pluripotency factor and ALKBH5 or ZNF217 expression was HIF-dependent. Immunohistochemistry revealed that expression of HIF-1α and ALKBH5 was concordant in all human breast cancer biopsies analyzed. ALKBH5 knockdown in MDA-MB-231 breast cancer cells significantly decreased metastasis from breast to lungs in immunodeficient mice. Thus, HIFs stimulate pluripotency factor expression and BCSC specification by negative regulation of RNA methylation. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 146 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Finland | 1 | <1% |
| Unknown | 145 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 39 | 27% |
| Researcher | 21 | 14% |
| Student > Bachelor | 17 | 12% |
| Student > Master | 12 | 8% |
| Student > Doctoral Student | 11 | 8% |
| Other | 13 | 9% |
| Unknown | 33 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 47 | 32% |
| Agricultural and Biological Sciences | 24 | 16% |
| Medicine and Dentistry | 20 | 14% |
| Immunology and Microbiology | 5 | 3% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
| Other | 8 | 5% |
| Unknown | 39 | 27% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 17 June 2021.
All research outputs
#6,169,729
of 22,886,568 outputs
Outputs from Oncotarget
#2,585
of 14,329 outputs
Outputs of similar age
#96,709
of 337,459 outputs
Outputs of similar age from Oncotarget
#187
of 1,213 outputs
Altmetric has tracked 22,886,568 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 14,329 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. 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 337,459 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 1,213 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.