Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04

AUTHORS

Anna A. Marusiak, Monika K. Prelowska, Dawid Mehlich, Michal Lazniewski, Klaudia Kaminska, Adam Gorczynski, Aleksandra Korwat, Olga Sokolowska, Hanna Kedzierska, Jakub Golab, Wojciech Biernat, Dariusz Plewczynski, John Brognard, Dominika Nowis

ABSTRACT

Metastasis to distant organs is a major cause for solid cancer mortality, and the acquisition of migratory and invasive phenotype is a key factor in initiation of malignancy. In this study we investigated the contribution of Mixed-Lineage Kinase 4 (MLK4) to aggressive phenotype of breast cancer cells. Our TCGA cancer genomic data analysis revealed that amplification or mRNA upregulation of MLK4 occurred in 23% of invasive breast carcinoma cases. To find the association between MLK4 expression and the specific subtype of breast cancer, we performed a transcriptomic analysis of multiple datasets, which showed that MLK4 is highly expressed in triple-negative breast cancer compared to other molecular subtypes. Depletion of MLK4 in cell lines with high MLK4 expression impaired proliferation and anchorage-dependent colony formation. Moreover, silencing of MLK4 expression significantly reduced the migratory potential and invasiveness of breast cancer cells as well as the number of spheroids formed in 3D cultures. These in vitro findings translate into slower rate of tumor growth in mice upon MLK4 knock-down. Furthermore, we established that MLK4 activates NF-κB signaling and promotes a mesenchymal phenotype in breast cancer cells. Immunohistochemical staining of samples obtained from breast cancer patients revealed a strong positive correlation between high expression of MLK4 and metastatic potential of tumors, which was predominantly observed in TNBC subgroup. Taken together, our results show that high expression of MLK4 promotes migratory and invasive phenotype of breast cancer and may represent a novel target for anticancer treatment. More... »

PAGES

1-16

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-018-0618-0

DOI

http://dx.doi.org/10.1038/s41388-018-0618-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1110634813

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30552384


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

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41388-018-0618-0'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41388-018-0618-0'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41388-018-0618-0'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41388-018-0618-0'


 

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290 https://www.grid.ac/institutes/grid.13339.3b schema:alternateName Medical University of Warsaw
291 schema:name Centre for Preclinical Research and Technology, Medical University of Warsaw, Warsaw, Poland
292 Department of Immunology, Medical University o``f Warsaw, Warsaw, Poland
293 Department of Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland
294 Genomic Medicine, Medical University of Warsaw, Warsaw, Poland
295 Laboratory of Experimental Medicine, Centre of New Technologies, University of Warsaw, Warsaw, Poland
296 Laboratory of Functional and Structural Genomics, Centre of New Technologies, University of Warsaw, Warsaw, Poland
297 Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
298 rdf:type schema:Organization
299 https://www.grid.ac/institutes/grid.48336.3a schema:alternateName National Cancer Institute
300 schema:name National Cancer Institute, Frederick, MD, USA
301 rdf:type schema:Organization
 




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