Prostate cancer is the most commonly diagnosed malignancy among men in industrialized countries, accounting for the second leading cause of cancer-related deaths. Although we now know that the androgen receptor (AR) is important for progression to the deadly advanced stages of the disease, it is poorly understood what AR-regulated processes drive this pathology. Here we demonstrate that AR regulates prostate cancer cell growth via the metabolic sensor 5'-AMP-activated protein kinase (AMPK), a kinase that classically regulates cellular energy homeostasis. In patients, activation of AMPK correlated with prostate cancer progression. Using a combination of radiolabeled assays and emerging metabolomic approaches, we also show that prostate cancer cells respond to androgen treatment by increasing not only rates of glycolysis, as is commonly seen in many cancers, but also glucose and fatty acid oxidation. Importantly, this effect was dependent on androgen-mediated AMPK activity. Our results further indicate that the AMPK-mediated metabolic changes increased intracellular ATP levels and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-mediated mitochondrial biogenesis, affording distinct growth advantages to the prostate cancer cells. Correspondingly, we used outlier analysis to determine that PGC-1α is overexpressed in a subpopulation of clinical cancer samples. This was in contrast to what was observed in immortalized benign human prostate cells and a testosterone-induced rat model of benign prostatic hyperplasia. Taken together, our findings converge to demonstrate that androgens can co-opt the AMPK-PGC-1α signaling cascade, a known homeostatic mechanism, to increase prostate cancer cell growth. The current study points to the potential utility of developing metabolic-targeted therapies directed toward the AMPK-PGC-1α signaling axis for the treatment of prostate cancer.Oncogene advance online publication, 4 November 2013; doi:10.1038/onc.2013.463.
Pharmacology, Toxicology and Pharmaceutical Science
4
3%
Immunology and Microbiology
3
2%
Other
10
7%
Unknown
33
24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 13. 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 11 October 2022.
All research outputs
#2,376,293
of 23,506,079 outputs
Outputs from Oncogene
#599
of 10,781 outputs
Outputs of similar age
#22,914
of 216,301 outputs
Outputs of similar age from Oncogene
#8
of 86 outputs
Altmetric has tracked 23,506,079 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,781 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one has done particularly well, scoring higher than 94% 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 216,301 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 89% of its contemporaries.
We're also able to compare this research output to 86 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 90% of its contemporaries.
