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MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib

Overview of attention for article published in Breast Cancer Research, December 2016
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (62nd percentile)
  • Above-average Attention Score compared to outputs of the same age and source (56th percentile)

Mentioned by

twitter
4 tweeters
facebook
1 Facebook page

Citations

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30 Dimensions

Readers on

mendeley
52 Mendeley
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Title
MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib
Published in
Breast Cancer Research, December 2016
DOI 10.1186/s13058-016-0781-6
Pubmed ID
Authors

Adelaide I. J. Young, Andrew M. K. Law, Lesley Castillo, Sabrina Chong, Hayley D. Cullen, Martin Koehler, Sebastian Herzog, Tilman Brummer, Erinna F. Lee, Walter D. Fairlie, Morghan C. Lucas, David Herrmann, Amr Allam, Paul Timpson, D. Neil Watkins, Ewan K. A. Millar, Sandra A. O’Toole, David Gallego-Ortega, Christopher J. Ormandy, Samantha R. Oakes, Young, Adelaide I J, Law, Andrew M K, Castillo, Lesley, Chong, Sabrina, Cullen, Hayley D, Koehler, Martin, Herzog, Sebastian, Brummer, Tilman, Lee, Erinna F, Fairlie, Walter D, Lucas, Morghan C, Herrmann, David, Allam, Amr, Timpson, Paul, Watkins, D Neil, Millar, Ewan K A, O'Toole, Sandra A, Gallego-Ortega, David, Ormandy, Christopher J, Oakes, Samantha R

Abstract

Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful. To examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells. MCL-1 inhibition caused apoptosis of basal-like MDA-MB-468-2A cells grown as monolayers, and sensitized them to the BCL-2/BCL-XL inhibitor ABT-263, demonstrating that MCL-1 regulated cell survival. In MDA-MB-231-2A cells, grown in an organotypic model, induction of BIMs2A produced an almost complete suppression of invasion. Apoptosis was induced in such a small proportion of these cells that it could not account for the large decrease in invasion, suggesting that MCL-1 was operating via a previously undetected mechanism. MCL-1 antagonism also suppressed local invasion and distant metastasis to the lung in mouse mammary intraductal xenografts. Kinomic profiling revealed that MCL-1 antagonism modulated Src family kinases and their targets, which suggested that MCL-1 might act as an upstream modulator of invasion via this pathway. Inhibition of MCL-1 in combination with dasatinib suppressed invasion in 3D models of invasion and inhibited the establishment of tumors in vivo. These data provide the first evidence that MCL-1 drives breast cancer cell invasion and suggests that MCL-1 antagonists could be used alone or in combination with drugs targeting Src kinases such as dasatinib to suppress metastasis.

Twitter Demographics

The data shown below were collected from the profiles of 4 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 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 2%
Unknown 51 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 19%
Student > Master 10 19%
Researcher 9 17%
Student > Bachelor 4 8%
Lecturer > Senior Lecturer 2 4%
Other 5 10%
Unknown 12 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 18 35%
Agricultural and Biological Sciences 6 12%
Pharmacology, Toxicology and Pharmaceutical Science 4 8%
Medicine and Dentistry 4 8%
Veterinary Science and Veterinary Medicine 1 2%
Other 3 6%
Unknown 16 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 20 December 2016.
All research outputs
#6,523,984
of 12,785,177 outputs
Outputs from Breast Cancer Research
#802
of 1,447 outputs
Outputs of similar age
#134,498
of 367,329 outputs
Outputs of similar age from Breast Cancer Research
#12
of 30 outputs
Altmetric has tracked 12,785,177 research outputs across all sources so far. This one is in the 48th percentile – i.e., 48% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,447 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.1. This one is in the 43rd percentile – i.e., 43% 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 367,329 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 62% of its contemporaries.
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 has gotten more attention than average, scoring higher than 56% of its contemporaries.