↓ Skip to main content

Oncotarget

Article Metrics

Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures

Overview of attention for article published in Oncotarget, December 2016
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (94th percentile)

Mentioned by

news
4 news outlets
twitter
3 tweeters

Citations

dimensions_citation
18 Dimensions

Readers on

mendeley
28 Mendeley
citeulike
2 CiteULike
Title
Src promotes castration-recurrent prostate cancer through androgen receptor-dependent canonical and non-canonical transcriptional signatures
Published in
Oncotarget, December 2016
DOI 10.18632/oncotarget.14401
Pubmed ID
Authors

Indranil Chattopadhyay, Jianmin Wang, Maochun Qin, Lingqiu Gao, Renae Holtz, Robert L. Vessella, Robert W. Leach, Irwin H. Gelman

Abstract

Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. Here, we show that activated Src (Src527F) induces androgen-independent growth in human LNCaP cells, concomitant with its ability to induce proliferation/survival genes normally induced by dihydrotestosterone (DHT) in androgen-dependent LNCaP and VCaP cells. Src induces additional gene signatures unique to CRPC cell lines, LNCaP-C4-2 and CWR22Rv1, and to CRPC LuCaP35.1 xenografts. By comparing the Src-induced AR-cistrome and/or transcriptome in LNCaP to those in CRPC and LuCaP35.1 tumors, we identified an 11-gene Src-regulated CRPC signature consisting of AR-dependent, AR binding site (ARBS)-associated genes whose expression is altered by DHT in LNCaP[Src527F] but not in LNCaP cells. The differential expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival, with the expression of BCAT1 required for Src-induced androgen-independent proliferation. Lastly, Src enhances AR binding to non-canonical ARBS enriched for FOXO1, TOP2B and ZNF217 binding motifs; cooperative AR/TOP2B binding to a non-canonical ARBS was both Src- and DHT-sensitive and correlated with increased levels of Src-induced phosphotyrosyl-TOP2B. These data suggest that CRPC progression is facilitated via Src-induced sensitization of AR to intracrine androgen levels, resulting in the engagement of canonical and non-canonical ARBS-dependent gene signatures.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 25%
Researcher 6 21%
Student > Bachelor 4 14%
Student > Master 3 11%
Professor 1 4%
Other 3 11%
Unknown 4 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 25%
Agricultural and Biological Sciences 6 21%
Medicine and Dentistry 3 11%
Pharmacology, Toxicology and Pharmaceutical Science 2 7%
Veterinary Science and Veterinary Medicine 1 4%
Other 4 14%
Unknown 5 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 29. 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 16 January 2017.
All research outputs
#355,385
of 8,919,425 outputs
Outputs from Oncotarget
#185
of 10,045 outputs
Outputs of similar age
#20,121
of 303,169 outputs
Outputs of similar age from Oncotarget
#24
of 421 outputs
Altmetric has tracked 8,919,425 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,045 research outputs from this source. They receive a mean Attention Score of 3.5. This one has done particularly well, scoring higher than 98% 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 303,169 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 421 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 94% of its contemporaries.