Evidence map›Paper›PMID 25051363›Full record

ArticleOncotarget2014

Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma.

Aparna Jayachandran, Matthew Anaka, Prashanth Prithviraj, Christopher Hudson, Sonja J McKeown, Pu-Han Lo, Laura J Vella, Colin R Goding, Jonathan Cebon, Andreas Behren

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 3% 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

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

  1. Pooled it
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  18. Dormancy of cutaneous melanoma.Cancer cell international · 2024
    Review
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29 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

10 authors at 3 institutions in 2 countries.

Aparna JayachandranLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia. Department of Medicine, University of Melbourne, Victoria, 3010, Australia.
Matthew AnakaLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia. Department of Medicine, University of Melbourne, Victoria, 3010, Australia.
Prashanth PrithvirajLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia. Department of Medicine, University of Melbourne, Victoria, 3010, Australia.
Christopher HudsonLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia.
Sonja J McKeownDepartment of Anatomy and Neuroscience, University of Melbourne, Victoria, 3010, Australia.
Pu-Han LoLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia.
Laura J VellaLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia. Department of Medicine, University of Melbourne, Victoria, 3010, Australia.
Colin R GodingLudwig Institute for Cancer Research, University of Oxford, Oxford, OX3 7DQ, UK.
Jonathan CebonLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia. Department of Medicine, University of Melbourne, Victoria, 3010, Australia.
Andreas BehrenLudwig Institute for Cancer Research, Melbourne-Austin Branch, Cancer Immunobiology Laboratory, Heidelberg, VIC 3084, Australia. Department of Medicine, University of Melbourne, Victoria, 3010, Australia.
University of Melbourne · AULudwig Cancer Research · AULudwig Cancer Research · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial-to-mesenchymal transition (EMT), in which epithelial cells loose their polarity and become motile mesenchymal cells, is a determinant of melanoma metastasis. We compared gene expression signatures of mesenchymal-like melanoma cells with those of epithelial-like melanoma cells, and identified Thrombospondin 1 (THBS1) as highly up-regulated in the mesenchymal phenotype. This study investigated whether THBS1, a major physiological activator of transforming growth factor (TGF)-beta, is involved in melanoma EMT-like process. We sought to examine expression patterns in distinct melanoma phenotypes including invasive, de-differentiated, label-retaining and drug resistant populations that are putatively associated with an EMT-like process. Here we show that THBS1 expression and secretion was elevated in melanoma cells exhibiting invasive, drug resistant, label retaining and mesenchymal phenotypes and correlated with reduced expression of genes involved in pigmentation. Elevated THBS1 levels were detected in Vemurafenib resistant melanoma cells and inhibition of THBS1 led to significantly reduced chemoresistance in melanoma cells. Notably, siRNA-mediated silencing of THBS1 and neutralizing antibody to THBS1 reduced invasion in mesenchymal-like melanoma cells, while ectopic THBS1 expression in epithelial-like melanoma cells enhanced invasion. Furthermore, the loss of THBS1 inhibited in vivo motility of melanoma cells within the embryonic chicken neural tube. In addition, we found aberrant THBS1 protein expression in metastatic melanoma tumor biopsies. These results implicate a role for THBS1 in EMT, and hence THBS1 may serve as a novel target for strategies aimed at the treatment of melanoma invasion and drug resistance.

Indexed as

AnimalsCell DifferentiationCell Line, TumorEpithelial-Mesenchymal TransitionGene ExpressionHeterograftsHumansMelanomaMicePhenotypeThrombospondin 1Thrombospondin 1

Identifiers

PMID25051363
PMCPMC4170613
OpenAlexW2138047179

What OpenQuestion 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 OpenQuestion graph.