Evidence map›Paper›PMID 31379747›Full record

ArticleFrontiers in endocrinology2019

Insulin Enhances Migration and Invasion in Prostate Cancer Cells by Up-Regulation of FOXC2.

Phoebe L Sarkar, Wendy Lee, Elizabeth D Williams, Amy A Lubik, Nataly Stylianou, Ali Shokoohmand, Melanie L Lehman, Brett G Hollier, Jennifer H Gunter, Colleen C Nelson

Open access · goldAbstract read
In one paragraph

Article in Frontiers in endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 27 citations in OpenAlex.

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  14. Super-enhancer Acquisition Drives FOXC2 Expression in Middle Ear Cholesteatoma.Journal of the Association for Research in Otolaryngology : JARO · 2021
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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

10 authors at 3 institutions in 2 countries.

Phoebe L SarkarQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Wendy LeeQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Elizabeth D WilliamsQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Amy A LubikVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Nataly StylianouQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Ali ShokoohmandQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Melanie L LehmanQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Brett G HollierQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Jennifer H GunterQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Colleen C NelsonQueensland University of Technology (QUT), Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Brisbane, QLD, Australia.
Queensland University of Technology · AUTranslational Research Institute · AUUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer (PCa), yet many patients relapse with lethal metastatic disease. With this loss of androgens, increased cell plasticity has been observed as an adaptive response to ADT. This includes gain of invasive and migratory capabilities, which may contribute to PCa metastasis. Hyperinsulinemia, which develops as a side-effect of ADT, has been associated with increased tumor aggressiveness and faster treatment failure. We investigated the direct effects of insulin in PCa cells that may contribute to this progression. We measured cell migration and invasion induced by insulin using wound healing and transwell assays in a range of PCa cell lines of variable androgen dependency (LNCaP, 22RV1, DuCaP, and DU145 cell lines). To determine the molecular events driving insulin-induced invasion we used transcriptomics, quantitative real time-PCR, and immunoblotting in three PCa cell lines. Insulin increased invasiveness of PCa cells, upregulating Forkhead Box Protein C2 (FOXC2), and activating key PCa cell plasticity mechanisms including gene changes consistent with epithelial-to-mesenchymal transition (EMT) and a neuroendocrine phenotype. Additionally, analysis of publicly available clinical PCa tumor data showed metastatic prostate tumors demonstrate a positive correlation between insulin receptor expression and the EMT transcription factor FOXC2. The insulin receptor is not suitable to target clinically however, our data shows that actions of insulin in PCa cells may be suppressed by inhibiting downstream signaling molecules, PI3K and ERK1/2. This study identifies for the first time, a mechanism for insulin-driven cancer cell motility and supports the concept that targeting insulin signaling at the level of the PCa tumor may extend the therapeutic efficacy of ADT.

Indexed as

androgen deprivationepithelial to mesenchymal transition (EMT)FOXC2hyperinsulinemiainvasionprostate cancer

Identifiers

PMID31379747
PMCPMC6652804
OpenAlexW2959197297

What Socratic 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 Socratic graph.