Glioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified: mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers.
Pharmacology, Toxicology and Pharmaceutical Science
4
5%
Neuroscience
4
5%
Other
5
6%
Unknown
19
25%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 25. 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 10 August 2015.
All research outputs
#1,652,400
of 27,776,330 outputs
Outputs from Stem Cell Reports
#478
of 2,243 outputs
Outputs of similar age
#19,147
of 283,344 outputs
Outputs of similar age from Stem Cell Reports
#13
of 46 outputs
Altmetric has tracked 27,776,330 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 2,243 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.3. This one has done well, scoring higher than 78% 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 283,344 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 93% of its contemporaries.
We're also able to compare this research output to 46 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 71% of its contemporaries.
