Evidence map›Paper›PMID 33652914›Full record

ArticleEntropy (Basel, Switzerland)2021

Coupled Feedback Loops Involving PAGE4, EMT and Notch Signaling Can Give Rise to Non-genetic Heterogeneity in Prostate Cancer Cells.

Divyoj Singh, Federico Bocci, Prakash Kulkarni, Mohit Kumar Jolly

Open access · goldAbstract read
In one paragraph

Article in Entropy (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
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

4 authors at 3 institutions in 2 countries.

Divyoj SinghCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
Federico BocciCenter for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA.
Prakash KulkarniDepartment of Medical Oncology and Experimental Therapeutics, City of Hope National Medical Center, Duarte, CA 91010, USA.
Mohit Kumar JollyCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India.
Indian Institute of Science Bangalore · INCity Of Hope National Medical Center · USUniversity of California, Irvine · US

Funding

Science and Engineering Research Board SB/S2/RJN-049/2018
6 · The paper itself

Abstract

Non-genetic heterogeneity is emerging as a crucial factor underlying therapy resistance in multiple cancers. However, the design principles of regulatory networks underlying non-genetic heterogeneity in cancer remain poorly understood. Here, we investigate the coupled dynamics of feedback loops involving (a) oscillations in androgen receptor (AR) signaling mediated through an intrinsically disordered protein PAGE4, (b) multistability in epithelial-mesenchymal transition (EMT), and c) Notch-Delta-Jagged signaling mediated cell-cell communication, each of which can generate non-genetic heterogeneity through multistability and/or oscillations. Our results show how different coupling strengths between AR and EMT signaling can lead to monostability, bistability, or oscillations in the levels of AR, as well as propagation of oscillations to EMT dynamics. These results reveal the emergent dynamics of coupled oscillatory and multi-stable systems and unravel mechanisms by which non-genetic heterogeneity in AR levels can be generated, which can act as a barrier to most existing therapies for prostate cancer patients.

Indexed as

androgen targeted therapyfeedback loopsintrinsically disordered proteinmultistabilitynon-genetic heterogeneityoscillationsPAGE4prostate cancer

Identifiers

PMID33652914
PMCPMC7996788
OpenAlexW3134155401

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.