Evidence map›Paper›PMID 33784590›Full record

ArticleNeoplasia (New York, N.Y.)2021

Embryonic protein NODAL regulates the breast tumor microenvironment by reprogramming cancer-derived secretomes.

Dylan Dieters-Castator, Paola M Dantonio, Matt Piaseczny, Guihua Zhang, Jiahui Liu, Miljan Kuljanin, Stephen Sherman, Michael Jewer, Katherine Quesnel, Eun Young Kang and 6 more

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

Article in Neoplasia (New York, N.Y.), 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 32% 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, 8 citations in OpenAlex.

  1. Article
  2. Article
  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

16 authors at 4 institutions in 1 country.

Dylan Dieters-CastatorDepartment of Anatomy and Cell Biology, Western University, London, ON, Canada.
Paola M DantonioDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Matt PiasecznyDepartment of Anatomy and Cell Biology, Western University, London, ON, Canada.
Guihua ZhangDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Jiahui LiuDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Miljan KuljaninRobarts Research Institute, London, ON, Canada; Department of Biochemistry, Western University, London, ON, Canada.
Stephen ShermanRobarts Research Institute, London, ON, Canada; Department of Physiology and Pharmacology, Western University, London, ON, Canada.
Michael JewerDepartment of Anatomy and Cell Biology, Western University, London, ON, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada.
Katherine QuesnelDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.
Eun Young KangDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
Martin KöbelDepartment of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
Gabrielle M SiegersDepartment of Oncology, University of Alberta, Edmonton, AB, Canada.
Andrew LeaskDepartment of Physiology and Pharmacology, Western University, London, ON, Canada.
David HessRobarts Research Institute, London, ON, Canada; Department of Physiology and Pharmacology, Western University, London, ON, Canada.
Gilles LajoieDepartment of Biochemistry, Western University, London, ON, Canada.
Lynne-Marie PostovitDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada; Department of Oncology, University of Alberta, Edmonton, AB, Canada. Electronic address: l.postovit@queensu.ca.
Western University · CAUniversity of Alberta · CAUniversity of Calgary · CAQueen's University · CA

Funding

CIHR PLS 9538CIHR PLS 95381
6 · The paper itself

Abstract

The tumor microenvironment (TME) is an important mediator of breast cancer progression. Cancer-associated fibroblasts constitute a major component of the TME and may originate from tissue-associated fibroblasts or infiltrating mesenchymal stromal cells (MSCs). The mechanisms by which cancer cells activate fibroblasts and recruit MSCs to the TME are largely unknown, but likely include deposition of a pro-tumorigenic secretome. The secreted embryonic protein NODAL is clinically associated with breast cancer stage and promotes tumor growth, metastasis, and vascularization. Herein, we show that NODAL expression correlates with the presence of activated fibroblasts in human triple-negative breast cancers and that it directly induces Cancer-associated fibroblasts phenotypes. We further show that NODAL reprograms cancer cell secretomes by simultaneously altering levels of chemokines (e.g., CXCL1), cytokines (e.g., IL-6) and growth factors (e.g., PDGFRA), leading to alterations in MSC chemotaxis. We therefore demonstrate a hitherto unappreciated mechanism underlying the dynamic regulation of the TME.

Indexed as

ActinsCancer-Associated FibroblastsCell Line, TumorChemokine CXCL1ChemotaxisFemaleHumansInterleukin-6Mesenchymal Stem CellsNodal ProteinPlatelet-Derived Growth FactorReceptor, Platelet-Derived Growth Factor alphaRNA InterferenceRNA, Small InterferingSignal TransductionTriple Negative Breast NeoplasmsACTA2 protein, humanActinsChemokine CXCL1CXCL1 protein, humanIL6 protein, humanInterleukin-6Nodal ProteinNODAL protein, humanPlatelet-Derived Growth Factorplatelet-derived growth factor AReceptor, Platelet-Derived Growth Factor alphaRNA, Small InterferingVascular Endothelial Growth Factor AVEGFA protein, humanBreast cancerMass spectrometryNODALProteomicsSecretome

Identifiers

PMID33784590
PMCPMC8041663
OpenAlexW3143578152

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.