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Mendeley readers
Attention Score in Context
| Title |
Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer
|
|---|---|
| Published in |
Cancer & Metabolism, October 2016
|
| DOI | 10.1186/s40170-016-0159-3 |
| Pubmed ID | |
| Authors |
Stephanie Sprowl-Tanio, Amber N. Habowski, Kira T. Pate, Miriam M. McQuade, Kehui Wang, Robert A. Edwards, Felix Grun, Yung Lyou, Marian L. Waterman |
| Abstract |
There is increasing evidence that oncogenic Wnt signaling directs metabolic reprogramming of cancer cells to favor aerobic glycolysis or Warburg metabolism. In colon cancer, this reprogramming is due to direct regulation of pyruvate dehydrogenase kinase 1 (PDK1) gene transcription. Additional metabolism genes are sensitive to Wnt signaling and exhibit correlative expression with PDK1. Whether these genes are also regulated at the transcriptional level, and therefore a part of a core metabolic gene program targeted by oncogenic WNT signaling, is not known. Here, we identify monocarboxylate transporter 1 (MCT-1; encoded by SLC16A1) as a direct target gene supporting Wnt-driven Warburg metabolism. We identify and validate Wnt response elements (WREs) in the proximal SLC16A1 promoter and show that they mediate sensitivity to Wnt inhibition via dominant-negative LEF-1 (dnLEF-1) expression and the small molecule Wnt inhibitor XAV939. We also show that WREs function in an independent and additive manner with c-Myc, the only other known oncogenic regulator of SLC16A1 transcription. MCT-1 can export lactate, the byproduct of Warburg metabolism, and it is the essential transporter of pyruvate as well as a glycolysis-targeting cancer drug, 3-bromopyruvate (3-BP). Using sulforhodamine B (SRB) assays to follow cell proliferation, we tested a panel of colon cancer cell lines for sensitivity to 3-BP. We observe that all cell lines are highly sensitive and that reduction of Wnt signaling by XAV939 treatment does not synergize with 3-BP, but instead is protective and promotes rapid recovery. We conclude that MCT-1 is part of a core Wnt signaling gene program for glycolysis in colon cancer and that modulation of this program could play an important role in shaping sensitivity to drugs that target cancer metabolism. |
Mendeley readers
The data shown below were compiled from readership statistics for 92 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 92 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 23 | 25% |
| Student > Master | 11 | 12% |
| Student > Bachelor | 11 | 12% |
| Researcher | 9 | 10% |
| Professor > Associate Professor | 5 | 5% |
| Other | 13 | 14% |
| Unknown | 20 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 31 | 34% |
| Agricultural and Biological Sciences | 16 | 17% |
| Medicine and Dentistry | 9 | 10% |
| Engineering | 3 | 3% |
| Computer Science | 3 | 3% |
| Other | 7 | 8% |
| Unknown | 23 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 06 October 2016.
All research outputs
#20,344,065
of 22,890,496 outputs
Outputs from Cancer & Metabolism
#183
of 205 outputs
Outputs of similar age
#278,358
of 321,456 outputs
Outputs of similar age from Cancer & Metabolism
#3
of 3 outputs
Altmetric has tracked 22,890,496 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 205 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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 321,456 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.