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Suppression of Spry4 enhances cancer stem cell properties of human MDA-MB-231 breast carcinoma cells

Overview of attention for article published in Cancer Cell International, March 2016
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Title
Suppression of Spry4 enhances cancer stem cell properties of human MDA-MB-231 breast carcinoma cells
Published in
Cancer Cell International, March 2016
DOI 10.1186/s12935-016-0292-7
Pubmed ID
Authors

Hongyu Jing, Lucy Liaw, Robert Friesel, Calvin Vary, Shucheng Hua, Xuehui Yang

Abstract

Cancer stem cells contribute to tumor initiation, heterogeneity, and recurrence, and are critical targets in cancer therapy. Sprouty4 (Spry4) is a potent inhibitor of signal transduction pathways elicited by receptor tyrosine kinases, and has roles in regulating cell proliferation, migration and differentiation. Spry4 has been implicated as a tumor suppressor and in modulating embryonic stem cells. The purpose of this research was to test the novel idea that Spry4 regulates cancer stem cell properties in breast cancer. Loss-of function of Spry4 in human MDA-MB-231 cell was used to test our hypothesis. Spry4 knockdown or control cell lines were generated using lentiviral delivery of human Spry4 or non-targeting control shRNAs, and then selected with 2 μg/ml puromycin. Cell growth and migratory abilities were determined using growth curve and cell cycle flow cytometry analyses and scratch assays, respectively. Xenograft tumor model was used to determine the tumorigenic activity and metastasis in vivo. Cancer stem cell related markers were evaluated using immunoblotting assays and fluorescence-activated cell sorting. Cancer stem cell phenotype was evaluated using in vitro mammosphere formation and drug sensitivity tests, and in vivo limiting dilution tumor formation assay. Two out of three tested human Spry4 shRNAs significantly suppressed the expression of endogenous Spry4 in MDA-MB-231 cells. Suppressing Spry4 expression increased MDA-MB-231 cell proliferation and migration. Suppressing Spry4 increased β3-integrin expression, and CD133(+)CD44(+) subpopulation. Suppressing Spry4 increased mammosphere formation, while decreasing the sensitivity of MDA-MB-231 cells to Paclitaxel treatment. Finally, suppressing Spry4 increased the potency of MDA-MB-231 cell tumor initiation, a feature attributed to cancer stem cells. Our findings provide novel evidence that endogenous Spry4 may have tumor suppressive activity in breast cancer by suppressing cancer stem cell properties in addition to negative effects on tumor cell proliferation and migration.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 29%
Professor 3 14%
Student > Bachelor 2 10%
Other 2 10%
Student > Master 2 10%
Other 4 19%
Unknown 2 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 43%
Medicine and Dentistry 4 19%
Agricultural and Biological Sciences 2 10%
Environmental Science 1 5%
Immunology and Microbiology 1 5%
Other 1 5%
Unknown 3 14%
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 15 March 2016.
All research outputs
#20,983,210
of 23,613,071 outputs
Outputs from Cancer Cell International
#1,429
of 1,869 outputs
Outputs of similar age
#254,831
of 300,985 outputs
Outputs of similar age from Cancer Cell International
#17
of 21 outputs
Altmetric has tracked 23,613,071 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,869 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 1st percentile – i.e., 1% 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 300,985 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.