↓ Skip to main content

Notch4 Signaling Induces a Mesenchymal–Epithelial–like Transition in Melanoma Cells to Suppress Malignant Behaviors

Overview of attention for article published in Cancer Research, March 2016
Altmetric Badge

Mentioned by

twitter
1 X user
facebook
1 Facebook page

Citations

dimensions_citation
46 Dimensions

Readers on

mendeley
42 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Notch4 Signaling Induces a Mesenchymal–Epithelial–like Transition in Melanoma Cells to Suppress Malignant Behaviors
Published in
Cancer Research, March 2016
DOI 10.1158/0008-5472.can-15-1722
Pubmed ID
Authors

Ehsan Bonyadi Rad, Heinz Hammerlindl, Christian Wels, Ulrich Popper, Dinoop Ravindran Menon, Heimo Breiteneder, Melitta Kitzwoegerer, Christine Hafner, Meenhard Herlyn, Helmut Bergler, Helmut Schaider

Abstract

The effects of Notch signaling are context-dependent and both oncogenic and tumor suppressive functions have been described. Notch signaling in melanoma is considered oncogenic, but clinical trials testing Notch inhibition in this malignancy have not proved successful. Here, we report that expression of the constitutively active intracellular domain of Notch4 (N4ICD) in melanoma cells triggered a switch from a mesenchymal-like parental phenotype to an epithelial-like phenotype. The epithelial-like morphology was accompanied by strongly reduced invasive, migratory, and proliferative properties concomitant with the downregulation of epithelial-mesenchymal transition markers Snail2 (SNAI2), Twist1, vimentin (VIM), and MMP2 and the re-expression of E-cadherin (CDH1). The N4ICD-induced phenotypic switch also resulted in significantly reduced tumor growth in vivo. Immunohistochemical analysis of primary human melanomas and cutaneous metastases revealed a significant correlation between Notch4 and E-cadherin expression. Mechanistically, we demonstrate that N4ICD induced the expression of the transcription factors Hey1 and Hey2, which bound directly to the promoter regions of Snail2 and Twist1 and repressed gene transcription, as determined by EMSA and luciferase assays. Taken together, our findings indicate a role for Notch4 as a tumor suppressor in melanoma, uncovering a potential explanation for the poor clinical efficacy of Notch inhibitors observed in this setting.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Finland 1 2%
France 1 2%
Unknown 40 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 21%
Researcher 8 19%
Student > Master 6 14%
Student > Bachelor 3 7%
Professor > Associate Professor 3 7%
Other 8 19%
Unknown 5 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 36%
Agricultural and Biological Sciences 10 24%
Medicine and Dentistry 6 14%
Immunology and Microbiology 2 5%
Chemistry 2 5%
Other 0 0%
Unknown 7 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 21 November 2017.
All research outputs
#18,345,259
of 23,577,654 outputs
Outputs from Cancer Research
#15,901
of 18,389 outputs
Outputs of similar age
#208,534
of 302,580 outputs
Outputs of similar age from Cancer Research
#210
of 273 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 18,389 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.1. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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 302,580 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 273 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.