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IRE1α-XBP1 pathway promotes melanoma progression by regulating IL-6/STAT3 signaling

Overview of attention for article published in Journal of Translational Medicine, February 2017
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (56th percentile)

Mentioned by

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4 tweeters
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1 Facebook page

Citations

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31 Dimensions

Readers on

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32 Mendeley
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Title
IRE1α-XBP1 pathway promotes melanoma progression by regulating IL-6/STAT3 signaling
Published in
Journal of Translational Medicine, February 2017
DOI 10.1186/s12967-017-1147-2
Pubmed ID
Authors

Cheng Chen, Xuejun Zhang

Abstract

The IRE1α-XBP1 pathway is the most conserved branch of the unfolded protein response pathways, which are activated during endoplasmic reticulum (ER) stress caused by the accumulation of unfolded/misfolded proteins in the ER lumen. The IRE1α-XBP1 pathway plays a critical role in various cancers. However, the role of this pathway in melanoma cell growth remains unclear. Sixty-one pairs of melanoma specimens and corresponding normal tissues from patients were stained with XBP1. Then, XBP1 splicing levels were detected in human tissues and cell lines at the mRNA level. IL-6 expression levels were determined in both melanocytes (HEMn-MP) and melanoma cells (Mel-RMu) overexpressing the spliced form of XBP1 (XBP1s). IL-6 expression was also examined in 4μ8C-treated HEMn-MP and Mel-RMu cells overexpressing IRE1α. Next, we analyzed potential XBP1s binding sites within the IL-6 promoter and conducted ChIP experiments. IL-6/STAT3 signaling was detected by western blotting. Melanoma cell proliferation was examined by CCK8 and BrdU assays. The mRNA and protein expression levels of XBP1s were significantly elevated in human melanoma tissues and cell lines compared with normal tissues or melanocytes, thus indicating the activation of the IRE1α-XBP1 branch in melanoma. Ectopic expression of IRE1α or XBP1s robustly enhanced IL-6 expression in HEMn-MP and Mel-RMu cells. Moreover, the inhibition of the RNase activity of IRE1α also abolished the effect of IRE1α in promoting IL-6 expression. Mechanistically, XBP1 binds the IL-6 promoter and activates its expression. Furthermore, secreted IL-6 functions in an autocrine/paracrine manner, activates the intracellular JAK/STAT3 pathway and promotes the proliferation of melanoma cells. Our results reveal that the IRE1α-XBP1 pathway regulates Mel-RMu cell proliferation and progression by activating IL-6/STAT3 signaling.

Twitter Demographics

The data shown below were collected from the profiles of 4 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 %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 19%
Student > Ph. D. Student 5 16%
Student > Bachelor 4 13%
Student > Doctoral Student 3 9%
Student > Postgraduate 3 9%
Other 2 6%
Unknown 9 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 28%
Medicine and Dentistry 5 16%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Agricultural and Biological Sciences 2 6%
Psychology 1 3%
Other 2 6%
Unknown 11 34%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 10 March 2017.
All research outputs
#7,943,723
of 15,054,760 outputs
Outputs from Journal of Translational Medicine
#975
of 2,858 outputs
Outputs of similar age
#111,430
of 260,859 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 2 outputs
Altmetric has tracked 15,054,760 research outputs across all sources so far. This one is in the 46th percentile – i.e., 46% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,858 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 64% 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 260,859 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 56% of its contemporaries.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them