Evidence map›Paper›PMID 34241740›Full record

ArticleBreast cancer research and treatment2021

Nonphosphorylatable PEA15 mutant inhibits epithelial-mesenchymal transition in triple-negative breast cancer partly through the regulation of IL-8 expression.

Jihyun Park, Moises J Tacam, Gaurav Chauhan, Evan N Cohen, Maria Gagliardi, Lakesla R Iles, Naoto T Ueno, Venkata L Battula, Yoo-Kyoung Sohn, Xiaoping Wang and 8 more

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

Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

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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

18 authors at 2 institutions in 2 countries.

Jihyun Park *Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Moises J Tacam *Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gaurav ChauhanSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Evan N CohenDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Maria GagliardiSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lakesla R IlesDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Naoto T UenoSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Venkata L BattulaSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yoo-Kyoung SohnDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Xiaoping WangSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hak-Sung KimDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Savitri KrishnamurthyDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Natalie W FowlkesDepartment of Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Morgan M GreenDepartment of Veterinary Medicine & Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Geoffrey A BartholomeuszDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Debu TripathyDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
James M ReubenDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chandra BartholomeuszSection of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. chbartho@mdanderson.org.ORCID http://orcid.org/0000-0002-5806-1557
The University of Texas MD Anderson Cancer Center · USKorea Advanced Institute of Science and Technology · KR

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Development of Targeted Therapy for ERK Pathway in Breast CancerR00CA139006 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BARTHOLOMEUSZ, CHANDRA · 2013 to 2015
$725k
Foundation for the National Institutes of Health P30CA016672Foundation for the National Institutes of Health R00CA139006NCI NIH HHS P30 CA016672NCI NIH HHS R00 CA139006University of Texas MD Anderson Cancer Center 111411-15
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks targeted therapies. Patients with TNBC have a very poor prognosis because the disease often metastasizes. New treatment approaches addressing drivers of metastasis and tumor growth are crucial to improving patient outcomes. Developing targeted gene therapy is thus a high priority for TNBC patients. PEA15 (phosphoprotein enriched in astrocytes, 15 kDa) is known to bind to ERK, preventing ERK from being translocated to the nucleus and hence blocking its activity. The biological function of PEA15 is tightly regulated by its phosphorylation at Ser104 and Ser116. However, the function and impact of phosphorylation status of PEA15 in the regulation of TNBC metastasis and in epithelial-to-mesenchymal transition (EMT) are not well understood.

methodsWe established stable cell lines overexpressing nonphosphorylatable (PEA15-AA) and phospho-mimetic (PEA15-DD) mutants. To dissect specific cellular mechanisms regulated by PEA15 phosphorylation status, we performed RT-PCR immune and metastasis arrays. In vivo mouse models were used to determine the effects of PEA15 phosphorylation on tumor growth and metastasis.

resultsWe found that the nonphosphorylatable mutant PEA15-AA prevented formation of mammospheres and expression of EMT markers in vitro and decreased tumor growth and lung metastasis in in vivo experiments when compared to control, PEA15-WT and phosphomimetic PEA15-DD. However, phosphomimetic mutant PEA15-DD promoted migration, mesenchymal marker expression, tumorigenesis, and lung metastasis in the mouse model. PEA15-AA-mediated inhibition of breast cancer cell migratory capacity and tumorigenesis was the partial result of decreased expression of interleukin-8 (IL-8). Further, we identified that expression of IL-8 was possibly mediated through one of the ERK downstream molecules, Ets-1.

conclusionsOur results show that PEA15 phosphorylation status serves as an important regulator for PEA15's dual role as an oncogene or tumor suppressor and support the potential of PEA15-AA as a therapeutic strategy for treatment of TNBC.

Indexed as

Epithelial-Mesenchymal TransitionTriple Negative Breast NeoplasmsAnimalsApoptosis Regulatory ProteinsCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansInterleukin-8MiceApoptosis Regulatory ProteinsInterleukin-8PEA15 protein, humanEMTEts-1IL-8PEA15Triple-negative breast cancer

Identifiers

PMID34241740
PMCPMC8357760
OpenAlexW3177938260

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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.