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Insulin-like growth factors are essential to prevent anoikis in oestrogen-responsive breast cancer cells: importance of the type I IGF receptor and PI3-kinase/Akt pathway

Overview of attention for article published in Molecular Cancer, January 2016
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Title
Insulin-like growth factors are essential to prevent anoikis in oestrogen-responsive breast cancer cells: importance of the type I IGF receptor and PI3-kinase/Akt pathway
Published in
Molecular Cancer, January 2016
DOI 10.1186/s12943-015-0482-2
Pubmed ID
Authors

Brendan C. Luey, Felicity E. B. May

Abstract

Detachment of epithelial cells from the extracellular matrix initiates programmed cell death by a process termed anoikis. Malignant cells must acquire anoikis resistance to leave the primary tumour and metastasise. Multiple signal transduction pathways can activate anoikis and confer anoikis resistance, but these are not understood in breast cancer. Models for anoikis of oestrogen-responsive breast cancer cells were established and the protective effects of IGF-1 tested. Cleaved PARP was measured by western transfer and cleaved caspase 3 by flow cytometry. Pathways involved in anoikis and in anoikis resistance were investigated with PI3-kinase, Akt, and MEK1 and MEK2 inhibitors. The importance of the type I IGF receptor was investigated by IGF-concentration dependence, siRNA knockdown and pharmacological inhibition. Association between IGF-1R expression and relapse with distant metastasis was analysed in 1609 patients by log rank test. Unattached breast cancer cells required culture in serum-free medium to induce anoikis. Rapid loss of FAK, Akt and Bad phosphorylation was concurrent with anoiks induction, but ERK1 and ERK2 phosphorylation increased which suggested that anoikis resistance is mediated by the PI3-kinase/Akt rather than the Grb2/Ras/MAP-kinase pathway. IGF-1 conferred anoikis resistance in serum-free medium. IGF-1 activated the PI3-kinase/Akt and Grb2/Ras/MAP-kinase pathways but experiments with PI3-kinase, Akt and MEK1 and MEK2 inhibitors showed that IGF protection is via the PI3-kinase/Akt pathway. The concentration dependence of IGF protection, knockdown experiments with siRNA and pharmacological inhibition with figitumumab, showed that IGF-1 signals through the type I IGF receptor. The crucial role of the type I IGF receptor was demonstrated by induction of anoikis in full serum by figitumumab. High IGF-1R expression was associated with reduced time to relapse with distant metastases in oestrogen receptor-positive patients, especially those with aggressive disease which confirms its relevance in vivo. Anoikis resistance of oestrogen-responsive breast cancer cells depends upon IGF activation of the type I IGF receptor and PI3-kinase/Akt pathway. Because IGF-dependent evasion of anoikis will facilitate metastasis by malignant breast cancer cells, effective inhibition of IGF signal transduction should be included in combinations of targeted drugs designed to treat metastatic oestrogen receptor-positive breast cancers.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 17%
Researcher 7 15%
Student > Master 7 15%
Student > Doctoral Student 2 4%
Professor > Associate Professor 2 4%
Other 6 13%
Unknown 15 32%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 19%
Agricultural and Biological Sciences 8 17%
Medicine and Dentistry 7 15%
Chemistry 3 6%
Unspecified 2 4%
Other 2 4%
Unknown 16 34%
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 24 January 2016.
All research outputs
#17,782,514
of 22,840,638 outputs
Outputs from Molecular Cancer
#1,203
of 1,721 outputs
Outputs of similar age
#268,888
of 395,188 outputs
Outputs of similar age from Molecular Cancer
#17
of 30 outputs
Altmetric has tracked 22,840,638 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 1,721 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 25th percentile – i.e., 25% 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 395,188 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
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 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.