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TNFα induces Ca2+ influx to accelerate extrinsic apoptosis in hepatocellular carcinoma cells

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, March 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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1 blog
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1 X user

Citations

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21 Mendeley
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Title
TNFα induces Ca2+ influx to accelerate extrinsic apoptosis in hepatocellular carcinoma cells
Published in
Journal of Experimental & Clinical Cancer Research, March 2018
DOI 10.1186/s13046-018-0714-6
Pubmed ID
Authors

Jianjun Zhu, Mingpeng Jin, Jiaojiao Wang, Hui Zhang, Yousheng Wu, Deyang Li, Xiaoying Ji, Hushan Yang, Chun Yin, Tingting Ren, Jinliang Xing

Abstract

Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved. The level of cytosolic Ca2+ was assessed by Fura-2 in HCC cells. After changing cytosolic Ca2+ level by using agonists or inhibitors, cell apoptosis was detected by flow cytometry. We also detected the effect of ionomycin or parvalbumin on the anti-tumor activity of TNFα in a mice model. Lastly, we studied the roles of cytosolic Ca2+ in the mitochondrial-dependent intrinsic apoptosis pathway. Here, we demonstrated that TNFα induced extracellular Ca2+ influx into cytoplasm through transient receptor potential channel in HCC cells. Both cytosolic Ca2+ scavenger and Ca2+-binding protein PV effectively desensitized hepatocellular carcinoma cells to TNFα, whereas combination ionomycin or 1,4,5-inositol triphosphate significantly sensitized HCC cells to TNFα, indicating that the increased level of cytosolic Ca2+ was positively correlated with the TNFα-induced cell apoptosis in vitro. In a nude mice xenograft model, our data revealed that TNFα combined with ionomycin remarkably synergized the anti-tumor effect of TNFα. Furthermore, we found that TNFα-mediated extracellular Ca2+ influx accelerated TNFα-induced extrinsic apoptosis through activating calpain/IAP/caspase3 pathway. Our study provides the evidence supporting a novel mechanism by which TNFα induces extracellular Ca2+ influx to enhance cell apoptosis and suggests that increasing the level of cytosolic Ca2+ might be an alternative strategy to improve the pro-apoptotic activity of TNFα in HCC cells, although suitable chemical or biological reagents need to be further tested.

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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 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 33%
Student > Bachelor 5 24%
Professor 1 5%
Lecturer 1 5%
Unknown 7 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 14%
Immunology and Microbiology 3 14%
Medicine and Dentistry 3 14%
Agricultural and Biological Sciences 1 5%
Arts and Humanities 1 5%
Other 2 10%
Unknown 8 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 11 March 2018.
All research outputs
#4,762,265
of 25,382,440 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#277
of 2,380 outputs
Outputs of similar age
#87,848
of 347,366 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#6
of 40 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,380 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 88% 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 347,366 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 74% of its contemporaries.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.