Evidence map›Paper›PMID 29059155›Full record

ArticleOncogene2018

Reactivation of androgen receptor-regulated lipid biosynthesis drives the progression of castration-resistant prostate cancer.

W Han, S Gao, D Barrett, M Ahmed, D Han, J A Macoska, H H He, C Cai

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 96 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

W HanCenter for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.
S GaoCenter for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.
D BarrettCenter for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.
M AhmedPrincess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
D HanCenter for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.
J A MacoskaCenter for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.
H H HePrincess Margaret Cancer Center/University Health Network, Toronto, Ontario, Canada.
C CaiCenter for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA.
University of Massachusetts Boston · USUniversity Health Network · CA

Funding

Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI KANTOFF, PHILIP W · 2002 to 2017
$36.2M
Molecular basis of androgen receptor mediated gene transcriptional repressionR00CA166507 · NCI · UNIVERSITY OF MASSACHUSETTS BOSTON · PI CAI, CHANGMENG · 2015 to 2017
$726k
NCI NIH HHS P50 CA090381NCI NIH HHS R00 CA166507
6 · The paper itself

Abstract

Androgen receptor (AR) is a transcriptional activator that, in prostate cells, stimulates gene expression required for various cellular functions, including metabolisms and proliferation. AR signaling is also essential for the development of hormone-dependent prostate cancer (PCa) and its activity can be blocked by androgen-deprivation therapies (ADTs). Although PCa patients initially respond well to ADTs, the cancer inevitably relapses and progresses to lethal castration-resistant prostate cancer (CRPC). Although AR activity is generally restored in CRPC despite the castrate level of androgens, it is unclear whether AR signaling is significantly reprogrammed. In this study, we examined the AR cistrome in a PCa cell line-derived CRPC model using integrated bioinformatical analyses. Significantly, we found that the AR cistrome is largely retained in the CRPC stage. In particular, AR-mediated lipid biosynthesis is highly conserved and reactivated during the progression to CRPC, and increased level of lipid synthesis is associated with poor prognosis. The restoration of lipid biosynthetic pathways is partially due to the increased expression of AR splice variants. Blocking lipid/cholesterol synthesis in AR variants-expressing CRPC cell line and xenograft models markedly reduces tumor growth through inhibition of mTOR pathway. Silencing the expression of a fatty acid elongase, ELOVL7, also leads to the regression of CRPC xenograft tumors. These results demonstrate the importance of reactivation of AR-regulated lipid biosynthetic pathways in driving CRPC progression, and suggest that ADTs may be therapeutically enhanced by blocking lipid biosynthetic pathways.

Indexed as

LipogenesisAcetyltransferasesAnimalsApoptosisBiomarkers, TumorCell ProliferationFatty Acid ElongasesHumansMaleMiceProstatic Neoplasms, Castration-ResistantReceptors, AndrogenSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysAcetyltransferasesAR protein, mouseBiomarkers, TumorELOVL7 protein, humanElovl7 protein, mouseFatty Acid ElongasesReceptors, Androgen

Identifiers

PMID29059155
PMCPMC5805650
OpenAlexW2766243515

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.