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CD38 is methylated in prostate cancer and regulates extracellular NAD+

Overview of attention for article published in Cancer & Metabolism, September 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#34 of 181)
  • Good Attention Score compared to outputs of the same age (79th percentile)

Mentioned by

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14 tweeters

Citations

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17 Dimensions

Readers on

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34 Mendeley
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Title
CD38 is methylated in prostate cancer and regulates extracellular NAD+
Published in
Cancer & Metabolism, September 2018
DOI 10.1186/s40170-018-0186-3
Pubmed ID
Authors

Jack Mottahedeh, Michael C. Haffner, Tristan R. Grogan, Takao Hashimoto, Preston D. Crowell, Himisha Beltran, Andrea Sboner, Rohan Bareja, David Esopi, William B. Isaacs, Srinivasan Yegnasubramanian, Matthew B. Rettig, David A. Elashoff, Elizabeth A. Platz, Angelo M. De Marzo, Michael A. Teitell, Andrew S. Goldstein

Abstract

Cancer cell metabolism requires sustained pools of intracellular nicotinamide adenine dinucleotide (NAD+) which is maintained by a balance of NAD+ hydrolase activity and NAD+ salvage activity. We recently reported that human prostate cancer can be initiated following oncogene expression in progenitor-like luminal cells marked by low expression of the NAD+-consuming enzyme CD38. CD38 expression is reduced in prostate cancer compared to benign prostate, suggesting that tumor cells may reduce CD38 expression in order to enhance pools of NAD+. However, little is known about how CD38 expression is repressed in advanced prostate cancer and whether CD38 plays a role in regulating NAD+ levels in prostate epithelial cells. CD38 expression, its association with recurrence after prostatectomy for clinically localized prostate cancer, and DNA methylation of the CD38 promoter were evaluated in human prostate tissues representing various stages of disease progression. CD38 was inducibly over-expressed in benign and malignant human prostate cell lines in order to determine the effects on cell proliferation and levels of NAD+ and NADH. NAD+ and NADH were also measured in urogenital tissues from wild-type and CD38 knockout mice. CD38 mRNA expression was reduced in metastatic castration-resistant prostate cancer compared to localized prostate cancer. In a large cohort of men undergoing radical prostatectomy, CD38 protein expression was inversely correlated with recurrence. We identified methylation of the CD38 promoter in primary and metastatic prostate cancer. Over-expression of wild-type CD38, but not an NAD+ hydrolase-deficient mutant, depleted extracellular NAD+ levels in benign and malignant prostate cell lines. However, expression of CD38 did not significantly alter intracellular NAD+ levels in human prostate cell lines grown in vitro and in urogenital tissues isolated from wild-type and CD38 knockout mice. CD38 protein expression in prostate cancer is associated with risk of recurrence. Methylation results suggest that CD38 is epigenetically regulated in localized and metastatic prostate cancer tissues. Our study provides support for CD38 as a regulator of extracellular, but not intracellular, NAD+ in epithelial cells. These findings suggest that repression of CD38 by methylation may serve to increase the availability of extracellular NAD+ in prostate cancer tissues.

Twitter Demographics

The data shown below were collected from the profiles of 14 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 18%
Student > Bachelor 5 15%
Student > Master 5 15%
Researcher 3 9%
Other 2 6%
Other 4 12%
Unknown 9 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 18%
Pharmacology, Toxicology and Pharmaceutical Science 4 12%
Medicine and Dentistry 4 12%
Immunology and Microbiology 3 9%
Sports and Recreations 1 3%
Other 4 12%
Unknown 12 35%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 02 November 2020.
All research outputs
#2,702,239
of 19,943,904 outputs
Outputs from Cancer & Metabolism
#34
of 181 outputs
Outputs of similar age
#58,445
of 291,921 outputs
Outputs of similar age from Cancer & Metabolism
#1
of 1 outputs
Altmetric has tracked 19,943,904 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 181 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. 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 291,921 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 79% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them