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Key regulators of lipid metabolism drive endocrine resistance in invasive lobular breast cancer

Overview of attention for article published in Breast Cancer Research, September 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (91st percentile)

Mentioned by

news
1 news outlet
twitter
26 tweeters

Citations

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49 Dimensions

Readers on

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50 Mendeley
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Title
Key regulators of lipid metabolism drive endocrine resistance in invasive lobular breast cancer
Published in
Breast Cancer Research, September 2018
DOI 10.1186/s13058-018-1041-8
Pubmed ID
Authors

Tian Du, Matthew J. Sikora, Kevin M. Levine, Nilgun Tasdemir, Rebecca B. Riggins, Stacy G. Wendell, Bennett Van Houten, Steffi Oesterreich

Abstract

Invasive lobular breast carcinoma (ILC) is a histological subtype of breast cancer that is characterized by loss of E-cadherin and high expression of estrogen receptor alpha (ERα). In many cases, ILC is effectively treated with adjuvant aromatase inhibitors (AIs); however, acquired AI resistance remains a significant problem. To identify underlying mechanisms of acquired anti-estrogen resistance in ILC, we recently developed six long-term estrogen-deprived (LTED) variant cell lines from the human ILC cell lines SUM44PE (SUM44; two lines) and MDA-MB-134VI (MM134; four lines). To better understand mechanisms of AI resistance in these models, we performed transcriptional profiling analysis by RNA-sequencing followed by candidate gene expression and functional studies. MM134 LTED cells expressed ER at a decreased level and lost growth response to estradiol, while SUM44 LTED cells retained partial ER activity. Our transcriptional profiling analysis identified shared activation of lipid metabolism across all six independent models. However, the underlying basis of this signature was distinct between models. Oxysterols were able to promote the proliferation of SUM44 LTED cells but not MM134 LTED cells. In contrast, MM134 LTED cells displayed a high expression of the sterol regulatory element-binding protein 1 (SREBP1), a regulator of fatty acid and cholesterol synthesis, and were hypersensitive to genetic or pharmacological inhibition of SREBPs. Several SREBP1 downstream targets involved in fatty acid synthesis, including FASN, were induced, and MM134 LTED cells were more sensitive to etomoxir, an inhibitor of the rate-limiting enzyme in beta-oxidation, than their respective parental control cells. Finally, in silico expression analysis in clinical specimens from a neo-adjuvant endocrine trial showed a significant association between the increase of SREBP1 expression and lack of clinical response, providing further support for a role of SREBP1 in the acquisition of endocrine resistance in breast cancer. Our characterization of a unique series of AI-resistant ILC models identifies the activation of key regulators of fatty acid and cholesterol metabolism, implicating lipid-metabolic processes driving estrogen-independent growth of ILC cells. Targeting these changes may prove a strategy for prevention and treatment of endocrine resistance for patients with ILC.

Twitter Demographics

The data shown below were collected from the profiles of 26 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 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 50 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 16%
Researcher 7 14%
Student > Bachelor 6 12%
Student > Doctoral Student 5 10%
Student > Ph. D. Student 5 10%
Other 9 18%
Unknown 10 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 26%
Medicine and Dentistry 11 22%
Agricultural and Biological Sciences 5 10%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Business, Management and Accounting 1 2%
Other 6 12%
Unknown 12 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 28. 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 18 July 2022.
All research outputs
#1,104,691
of 21,821,479 outputs
Outputs from Breast Cancer Research
#91
of 1,855 outputs
Outputs of similar age
#24,864
of 297,024 outputs
Outputs of similar age from Breast Cancer Research
#1
of 1 outputs
Altmetric has tracked 21,821,479 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,855 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.8. This one has done particularly well, scoring higher than 95% 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 297,024 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 91% of its contemporaries.
We're also able to compare this research output to 1 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