Evidence map›Paper›PMID 33941680›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

Abhijeet P Deshmukh, Suhas V Vasaikar, Katarzyna Tomczak, Shubham Tripathi, Petra den Hollander, Emre Arslan, Priyanka Chakraborty, Rama Soundararajan, Mohit Kumar Jolly, Kunal Rai and 2 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed
17.7field-weighted citation impact, top 1% 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

175 citing papers in PubMed, 262 citations in OpenAlex.

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

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 3 institutions in 2 countries.

Abhijeet P DeshmukhDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.ORCID 0000-0002-3587-8812
Suhas V VasaikarDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Katarzyna TomczakDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030.ORCID 0000-0003-0553-8056
Shubham TripathiCenter for Theoretical Biological Physics, Northeastern University, Boston, MA 02115.ORCID 0000-0002-0141-987X
Petra den HollanderDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Emre ArslanDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
Priyanka ChakrabortyCentre for BioSystems Science and Engineering, Indian Institute of Science, 560012 Bangalore, India.
Rama SoundararajanDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.ORCID 0000-0001-6976-3784
Mohit Kumar JollyCentre for BioSystems Science and Engineering, Indian Institute of Science, 560012 Bangalore, India.ORCID 0000-0002-6631-2109
Kunal RaiDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030; krai@mdanderson.org h.levine@northeastern.edu Smani@mdanderson.org.
Herbert LevineCenter for Theoretical Biological Physics, Northeastern University, Boston, MA 02115; krai@mdanderson.org h.levine@northeastern.edu Smani@mdanderson.org.ORCID 0000-0002-8819-9055
Sendurai A ManiDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030; krai@mdanderson.org h.levine@northeastern.edu Smani@mdanderson.org.ORCID 0000-0002-5918-4276
The University of Texas MD Anderson Cancer Center · USIndian Institute of Science Bangalore · INNortheastern University · US

Funding

Pleiotropic functions of FOXC2 in EMT, stem cells and breast cancer progressionR01CA155243 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MANI, SENDURAI AYYAVOO · 2011 to 2022
$3.2M
Preclinical characterization of EMT/CSC-specific small molecule inhibitors for TNBCsR01CA200970 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LAIRSON, LUKE LEE, MANI, SENDURAI AYYAVOO · 2017 to 2021
$2.7M
Role of UBR7, a novel H2BK120 E3 ubiquitin ligase, in suppression of breast cancerR01CA226269 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI RAI, KUNAL · 2020 to 2024
$1.8M
NCI NIH HHS R01 CA155243NCI NIH HHS R01 CA200970NCI NIH HHS R01 CA226269
6 · The paper itself

Abstract

The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-β, BMP, Wnt-β-catenin, NOTCH, Shh, and receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing EMT by TGF-β1 stimulation. Our comprehensive analysis revealed that cells progress through EMT at different paces. Using pseudotime clustering reconstruction of gene-expression profiles during EMT, we found sequential and parallel activation of EMT signaling pathways. We also observed various transitional cellular states during EMT. We identified regulatory signaling nodes that drive EMT with the expression of important microRNAs and transcription factors. Using a random circuit perturbation methodology, we demonstrate that the NOTCH signaling pathway acts as a key driver of TGF-β-induced EMT. Furthermore, we demonstrate that the gene signatures of pseudotime clusters corresponding to the intermediate hybrid EMT state are associated with poor patient outcome. Overall, this study provides insight into context-specific drivers of cancer progression and highlights the complexities of the EMT process.

Indexed as

Gene Regulatory NetworksCell LineEpithelial CellsEpithelial-Mesenchymal TransitionGene Expression ProfilingHumansKaplan-Meier EstimateMicroRNAsNeoplasmsPrognosisProportional Hazards ModelsRNA-SeqSignal TransductionSingle-Cell AnalysisTransforming Growth Factor beta1MicroRNAsTransforming Growth Factor beta1EMTNOTCHRACIPEscRNA-seqsignaling cascade

Identifiers

PMID33941680
PMCPMC8126782
OpenAlexW3157197874

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.