The unfolded protein response impacts melanoma progression by enhancing FGF expression and can be antagonized by a chemical chaperone View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Karin Eigner, Yüksel Filik, Florian Mark, Birgit Schütz, Günter Klambauer, Richard Moriggl, Markus Hengstschläger, Herbert Stangl, Mario Mikula, Clemens Röhrl

ABSTRACT

The mechanisms hallmarking melanoma progression are insufficiently understood. Here we studied the impact of the unfolded protein response (UPR) - a signalling cascade playing ambiguous roles in carcinogenesis - in melanoma malignancy. We identified isogenic patient-derived melanoma cell lines harboring BRAFV600E-mutations as a model system to study the role of intrinsic UPR in melanoma progression. We show that the activity of the three effector pathways of the UPR (ATF6, PERK and IRE1) was increased in metastatic compared to non-metastatic cells. Increased UPR-activity was associated with increased flexibility to cope with ER stress. The activity of the ATF6- and the PERK-, but not the IRE-pathway, correlated with poor survival in melanoma patients. Using whole-genome expression analysis, we show that the UPR is an inducer of FGF1 and FGF2 expression and cell migration. Antagonization of the UPR using the chemical chaperone 4-phenylbutyric acid (4-PBA) reduced FGF expression and inhibited cell migration and viability. Consistently, FGF expression positively correlated with the activity of ATF6 and PERK in human melanomas. We conclude that chronic UPR stimulates the FGF/FGF-receptor signalling axis and promotes melanoma progression. Hence, the development of potent chemical chaperones to antagonize the UPR might be a therapeutic approach to target melanoma. More... »

PAGES

17498

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-17888-9

DOI

http://dx.doi.org/10.1038/s41598-017-17888-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1099597891

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29235576


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-017-17888-9'

N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-017-17888-9'


 

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291 Medical University of Vienna, Vienna, Austria
292 rdf:type schema:Organization
293 https://www.grid.ac/institutes/grid.9970.7 schema:alternateName Johannes Kepler University of Linz
294 schema:name Institute of Bioinformatics, Johannes Kepler University, Linz, Austria
295 rdf:type schema:Organization
 




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