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Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response

Overview of attention for article published in Breast Cancer Research, January 2013
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)
  • High Attention Score compared to outputs of the same age and source (86th percentile)

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2 X users
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4 patents

Citations

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191 Dimensions

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182 Mendeley
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Title
Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response
Published in
Breast Cancer Research, January 2013
DOI 10.1186/bcr3373
Pubmed ID
Authors

Anika Nagelkerke, Johan Bussink, Hilda Mujcic, Bradly G Wouters, Steffi Lehmann, Fred CGJ Sweep, Paul N Span

Abstract

ABSTRACT: INTRODUCTION: The hypoxia-inducible factor (HIF)-1 pathway can stimulate tumor cell migration and metastasis. Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, the unfolded protein response (UPR) is also induced by hypoxic conditions. The PKR-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-arm of the UPR induces expression of lysosomal-associated membrane protein 3 (LAMP3), a factor that has been linked to metastasis and poor prognosis in solid tumors. In this study the role of UPR-induced LAMP3 in hypoxia-mediated migration of breast cancer cells was examined. METHODS: A number of in vitro metastasis models were used to study the migration and invasion of MDA-MB-231 breast cancer cells under hypoxic conditions. PERK, ATF4 and their downstream factor LAMP3 were knocked down to examine their role in cell migration. In addition, multicellular tumor spheroids were used to study the involvement of the tumor microenvironment in invasion. RESULTS: Using transwell assays, migration of different breast cancer cell lines was assessed. A direct correlation was found between cell migration and baseline LAMP3 expression. Furthermore, moderate hypoxia (1% O2) was found to be optimal in stimulating migration of MDA-MB-231 cells. siRNA mediated knockdown of PERK, ATF4 and LAMP3 reduced migration of cells under these conditions. Using gap closure assays, similar results were found. In a three-dimensional invasion assay into collagen, LAMP3 knockdown cells showed a diminished capacity to invade compared to control cells when collectively grown in multicellular spheroids. CONCLUSIONS: Thus, the PERK/ATF4/LAMP3-arm of the UPR is an additional pathway mediating hypoxia-induced breast cancer cell migration.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users 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 182 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 1%
Belgium 1 <1%
India 1 <1%
Greece 1 <1%
Spain 1 <1%
Unknown 176 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 46 25%
Researcher 29 16%
Student > Master 25 14%
Student > Bachelor 16 9%
Student > Doctoral Student 14 8%
Other 13 7%
Unknown 39 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 51 28%
Biochemistry, Genetics and Molecular Biology 46 25%
Medicine and Dentistry 22 12%
Engineering 7 4%
Chemistry 5 3%
Other 10 5%
Unknown 41 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 14 June 2022.
All research outputs
#3,415,510
of 25,374,917 outputs
Outputs from Breast Cancer Research
#378
of 2,053 outputs
Outputs of similar age
#33,140
of 289,579 outputs
Outputs of similar age from Breast Cancer Research
#2
of 22 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,053 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one has done well, scoring higher than 80% 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 289,579 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.