Evidence map›Paper›PMID 26871947›Full record

ArticleOncotarget2016

Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA-/lo castration-resistant cells.

Kiera Rycaj, Eun Jeong Cho, Xin Liu, Hsueh-Ping Chao, Bigang Liu, Qiuhui Li, Ashwini K Devkota, Dingxiao Zhang, Xin Chen, John Moore and 2 more

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

20 citing papers in PubMed, 23 citations in OpenAlex.

  1. Trial
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  6. Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024
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  16. Tumor Dormancy and Slow-Cycling Cancer Cells.Advances in experimental medicine and biology · 2019
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 2 countries.

Kiera RycajDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Eun Jeong ChoCollege of Pharmacy, Targeted Therapeutic Drug Discovery and Development Core Facility (TTDDD), The University of Texas at Austin, Austin, TX 78712, USA.
Xin LiuDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Hsueh-Ping ChaoDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Bigang LiuDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Qiuhui LiDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Ashwini K DevkotaCollege of Pharmacy, Targeted Therapeutic Drug Discovery and Development Core Facility (TTDDD), The University of Texas at Austin, Austin, TX 78712, USA.
Dingxiao ZhangDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Xin ChenDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
John MooreDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
Kevin N DalbyCollege of Pharmacy, Targeted Therapeutic Drug Discovery and Development Core Facility (TTDDD), The University of Texas at Austin, Austin, TX 78712, USA.
Dean G TangDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
The University of Texas MD Anderson Cancer Center · USThe University of Texas at Austin · US

Funding

RESEARCH TRAINING IN CARCINOGENESIS &MUTAGENESIST32CA009480 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RICHIE, ELLEN R · 1985 to 2012
$3.0M
Decoding NanogP8 in TumorigenesisR01CA155693 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI TANG, DEAN G. · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA155693NCI NIH HHS T32 CA009480
6 · The paper itself

Abstract

We have recently demonstrated that the undifferentiated PSA-/lo prostate cancer (PCa) cell population harbors self-renewing long-term tumor-propagating cells that are refractory to castration, thus representing a therapeutic target. Our goals here are, by using the same lineage-tracing reporter system, to track the dynamic changes of PSA-/lo and PSA+ cells upon castration in vitro, investigate the molecular changes accompanying persistent castration, and develop large numbers of PSA-/lo PCa cells for drug screening. To these ends, we treated LNCaP cells infected with the PSAP-GFP reporter with three regimens of castration, i.e., CDSS, CDSS plus bicalutamide, and MDV3100 continuously for up to ~21 months. We observed that in the first ~7 months, castration led to time-dependent increases in PSA-/lo cells, loss of AR and PSA expression, increased expression of cancer stem cell markers, and many other molecular changes. Meanwhile, castrated LNCaP cells became resistant to high concentrations of MDV3100, chemotherapeutic drugs, and other agents. However, targeted and medium-throughput library screening identified several kinase (e.g., IGF-1R, AKT, PI3K/mTOR, Syk, GSK3) inhibitors as well as the BCL2 inhibitor that could effectively sensitize the LNCaP-CRPC cells to killing. Of interest, LNCaP cells castrated for >7 months showed evidence of cyclic changes in AR and the mTOR/AKT signaling pathways potentially involving epigenetic mechanisms. These observations indicate that castration elicits numerous molecular changes and leads to enrichment of PSA-/lo PCa cells. The ability to generate large numbers of PSA-/lo PCa cells should allow future high-throughput screening to identify novel therapeutics that specifically target this population.

Indexed as

Antineoplastic AgentsApoptosisBiomarkers, TumorCell CycleCell MovementCell ProliferationHumansLongitudinal StudiesMaleProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantProtein Kinase InhibitorsTumor Cells, CulturedAntineoplastic AgentsBiomarkers, TumorProstate-Specific AntigenProtein Kinase Inhibitorscancer stem cellscastration resistancecellular heterogeneitydifferentiationprostate cancer

Identifiers

PMID26871947
PMCPMC4924710
OpenAlexW2290591211

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.