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SOX5 is involved in balanced MITF regulation in human melanoma cells

Overview of attention for article published in BMC Medical Genomics, January 2016
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2 tweeters

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Title
SOX5 is involved in balanced MITF regulation in human melanoma cells
Published in
BMC Medical Genomics, January 2016
DOI 10.1186/s12920-016-0170-0
Pubmed ID
Authors

Kordaß, Theresa, Weber, Claudia E M, Oswald, Marcus, Ast, Volker, Bernhardt, Mathias, Novak, Daniel, Utikal, Jochen, Eichmüller, Stefan B, König, Rainer, Theresa Kordaß, Claudia E. M. Weber, Marcus Oswald, Volker Ast, Mathias Bernhardt, Daniel Novak, Jochen Utikal, Stefan B. Eichmüller, Rainer König

Abstract

Melanoma is a cancer with rising incidence and new therapeutics are needed. For this, it is necessary to understand the molecular mechanisms of melanoma development and progression. Melanoma differs from other cancers by its ability to produce the pigment melanin via melanogenesis; this biosynthesis is essentially regulated by microphthalmia-associated transcription factor (MITF). MITF regulates various processes such as cell cycling and differentiation. MITF shows an ambivalent role, since high levels inhibit cell proliferation and low levels promote invasion. Hence, well-balanced MITF homeostasis is important for the progression and spread of melanoma. Therefore, it is difficult to use MITF itself for targeted therapy, but elucidating its complex regulation may lead to a promising melanoma-cell specific therapy. We systematically analyzed the regulation of MITF with a novel established transcription factor based gene regulatory network model. Starting from comparative transcriptomics analysis using data from cells originating from nine different tumors and a melanoma cell dataset, we predicted the transcriptional regulators of MITF employing ChIP binding information from a comprehensive set of databases. The most striking regulators were experimentally validated by functional assays and an MITF-promoter reporter assay. Finally, we analyzed the impact of the expression of the identified regulators on clinically relevant parameters of melanoma, i.e. the thickness of primary tumors and patient overall survival. Our model predictions identified SOX10 and SOX5 as regulators of MITF. We experimentally confirmed the role of the already well-known regulator SOX10. Additionally, we found that SOX5 knockdown led to MITF up-regulation in melanoma cells, while double knockdown with SOX10 showed a rescue effect; both effects were validated by reporter assays. Regarding clinical samples, SOX5 expression was distinctively up-regulated in metastatic compared to primary melanoma. In contrast, survival analysis of melanoma patients with predominantly metastatic disease revealed that low SOX5 levels were associated with a poor prognosis. MITF regulation by SOX5 has been shown only in murine cells, but not yet in human melanoma cells. SOX5 has a strong inhibitory effect on MITF expression and seems to have a decisive clinical impact on melanoma during tumor progression.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Denmark 1 3%
Unknown 31 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 22%
Student > Ph. D. Student 5 16%
Student > Bachelor 5 16%
Researcher 3 9%
Other 3 9%
Other 6 19%
Unknown 3 9%
Readers by discipline Count As %
Agricultural and Biological Sciences 12 38%
Biochemistry, Genetics and Molecular Biology 6 19%
Computer Science 3 9%
Medicine and Dentistry 3 9%
Engineering 2 6%
Other 3 9%
Unknown 3 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 March 2016.
All research outputs
#13,460,530
of 22,852,911 outputs
Outputs from BMC Medical Genomics
#501
of 1,223 outputs
Outputs of similar age
#189,613
of 393,602 outputs
Outputs of similar age from BMC Medical Genomics
#17
of 30 outputs
Altmetric has tracked 22,852,911 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,223 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 56% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 393,602 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 30 others from the same source and published within six weeks on either side of this one. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.