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A co-culture genome-wide RNAi screen with mammary epithelial cells reveals transmembrane signals required for growth and differentiation

Overview of attention for article published in Breast Cancer Research, January 2015
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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 (80th percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

Mentioned by

twitter
5 tweeters
patent
1 patent

Citations

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22 Dimensions

Readers on

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73 Mendeley
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Title
A co-culture genome-wide RNAi screen with mammary epithelial cells reveals transmembrane signals required for growth and differentiation
Published in
Breast Cancer Research, January 2015
DOI 10.1186/s13058-014-0510-y
Pubmed ID
Authors

Angela Burleigh, Steven McKinney, Jazmine Brimhall, Damian Yap, Peter Eirew, Steven Poon, Viola Ng, Adrian Wan, Leah Prentice, Lois Annab, J Carl Barrett, Carlos Caldas, Connie Eaves, Samuel Aparicio

Abstract

IntroductionThe extracellular signals regulating mammary epithelial cell growth are of relevance to understanding the pathophysiology of mammary epithelia, yet they remain poorly characterized. Here we applied an unbiased approach to understanding the functional role of signaling molecules in several models of normal physiological growth and translated these results to the biological understanding of breast cancer subtypes.MethodsWe developed and utilized a cytogenetically normal clonal line of hTERT immortalized human mammary epithelial cells in a fibroblast-enhanced co-culture assay to conduct a genome-wide siRNA screen evaluating the functional effect of silencing each gene. Our selection endpoint was inhibition of growth. Rigorous post-screen validation processes including RT-QPCR to ensure on-target silencing, deconvolution of pooled siRNAs, and independent confirmation of effects with lentiviral shRNA constructs, identified a subset of genes required for mammary epithelial cell growth. Using three-dimensional (3D) Matrigel growth/differentiation assays and primary human mammary epithelial cell colony assays, we confirm that these growth effects are not limited to the 184hTERT cell line. We utilized the METABRIC dataset of 1,998 breast cancer patients to evaluate both the differential expression of these genes across breast cancer subtypes and their prognostic significance.ResultsWe identified 47 genes that are critically important for fibroblast-enhanced mammary epithelial cell growth. This group was enriched for several axonal guidance molecules and GPCRs, as well as the endothelin receptor, PROCR. The majority (43 out of 47) of genes identified in 2D were also required for 3D growth, with HSD17B2, SNN, and PROCR showing greater than 10-fold reductions in acinar formation. Several genes, including PROCR and the neuronal pathfinding molecules EFNA4 and NTN1, were also required for proper differentiation/polarization in 3D cultures. The 47 genes identified show a significant non-random enrichment for differential expression among 10 molecular subtypes of breast cancer, sampled from 1,998 patients. CD79A, SERPINH1, KCNJ5, and TMEM14C exhibit breast cancer subtype-independent overall survival differences.ConclusionDiverse transmembrane signals are required for mammary epithelial cell growth in 2D and 3D conditions. Strikingly, we define novel roles for axonal pathfinding receptors and ligands and the endothelin receptor in both growth and differentiation.

Twitter Demographics

The data shown below were collected from the profiles of 5 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 73 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 73 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 23 32%
Other 15 21%
Student > Master 10 14%
Student > Ph. D. Student 9 12%
Student > Bachelor 3 4%
Other 6 8%
Unknown 7 10%
Readers by discipline Count As %
Agricultural and Biological Sciences 34 47%
Medicine and Dentistry 8 11%
Biochemistry, Genetics and Molecular Biology 7 10%
Engineering 4 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 10 14%
Unknown 8 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 17 March 2021.
All research outputs
#4,070,419
of 20,501,648 outputs
Outputs from Breast Cancer Research
#530
of 1,822 outputs
Outputs of similar age
#65,037
of 336,579 outputs
Outputs of similar age from Breast Cancer Research
#5
of 36 outputs
Altmetric has tracked 20,501,648 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,822 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.3. This one has gotten more attention than average, scoring higher than 70% 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 336,579 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 80% of its contemporaries.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.