Evidence map›Paper›PMID 23334323›Full record

ArticleOncogene2014

Nodal promotes invasive phenotypes via a mitogen-activated protein kinase-dependent pathway.

D F Quail, G Zhang, S D Findlay, D A Hess, L-M Postovit

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

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 51 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

5 authors at 1 institution in 1 country.

D F QuailDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
G Zhang1] Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada [2] Robarts Research Institute, University of Western Ontario, London, ON, Canada.
S D Findlay1] Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada [2] Robarts Research Institute, University of Western Ontario, London, ON, Canada.
D A Hess1] Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada [2] Robarts Research Institute, University of Western Ontario, London, ON, Canada.
L-M Postovit1] Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada [2] Robarts Research Institute, University of Western Ontario, London, ON, Canada.
Western University · CA

Funding

CIHR 119589-1CIHR 89714-1CIHR 95381-1CIHR MOP 119589CIHR MOP 89714CIHR PLS 95381
6 · The paper itself

Abstract

The progression of cancer from localized to invasive disease is requisite for metastasis, and is often characterized by epithelial-to-mesenchymal transition (EMT) and alterations in cellular adhesion and migration. Studies have shown that this transition is associated with an upregulation of embryonic stem cell-associated genes, resulting in a dedifferentiated phenotype and poor patient prognosis. Nodal is an embryonic factor that plays a critical role in promoting early invasive events during development. Nodal is silenced as stem cells differentiate; however, it re-emerges in adult life during placentation and mammary gland development, and is aberrantly expressed in many cancers. Here, we show that Nodal overexpression, in poorly invasive breast cancer and choriocarcinoma cells, causes increased invasion and migration in vitro. Furthermore, we show that Nodal overexpression in these epithelial cancer types induces an EMT-like event concomitant with the internalization of E-Cadherin. This ability of Nodal to promote cellular invasion and EMT-like phenomena is dependent upon the phosphorylation of ERK1/2. As Nodal normally signals through SMADs, these findings lend insight into an alternative pathway that is hijacked by this protein in cancer. To evaluate the clinical implications of our results, we show that Nodal inhibition reduces liver tumor burden in a model of spontaneous breast cancer metastasis in vivo, and that Nodal loss-of-function in aggressive breast cancer lines results in a decrease in invasive phenotypes. Our results demonstrate that Nodal is involved in promoting invasion in multiple cellular contexts, and that Nodal inhibition may be useful as a therapeutic target for patients with progressive disease.

Indexed as

AnimalsBlotting, WesternCell Line, TumorCell MovementCell SurvivalEpithelial-Mesenchymal TransitionFluorescent Antibody TechniqueHeterograftsHumansMAP Kinase Signaling SystemMiceNeoplasm InvasivenessNodal ProteinPhenotypeReal-Time Polymerase Chain ReactionTransfectionNodal ProteinNODAL protein, human

Identifiers

PMID23334323
PMCPMC5025281
OpenAlexW1984475561

What OpenQuestion holds

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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.