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000126257 0247_ $$2doi$$a10.1016/j.stemcr.2015.03.005
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000126257 1001_ $$aCheng, Peng$$b0
000126257 245__ $$aKinome-wide shRNA screen identifies the receptor tyrosine kinase AXL as a key regulator for mesenchymal glioblastoma stem-like cells.
000126257 260__ $$aMaryland Heights, MO$$bCell Press$$c2015
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000126257 520__ $$aGlioblastoma is a highly lethal cancer for which novel therapeutics are urgently needed. Two distinct subtypes of glioblastoma stem-like cells (GSCs) were recently identified: mesenchymal (MES) and proneural (PN). To identify mechanisms to target the more aggressive MES GSCs, we combined transcriptomic expression analysis and kinome-wide short hairpin RNA screening of MES and PN GSCs. In comparison to PN GSCs, we found significant upregulation and phosphorylation of the receptor tyrosine kinase AXL in MES GSCs. Knockdown of AXL significantly decreased MES GSC self-renewal capacity in vitro and inhibited the growth of glioblastoma patient-derived xenografts. Moreover, inhibition of AXL with shRNA or pharmacologic inhibitors also increased cell death significantly more in MES GSCs. Clinically, AXL expression was elevated in the MES GBM subtype and significantly correlated with poor prognosis in multiple cancers. In conclusion, we identified AXL as a potential molecular target for novel approaches to treat glioblastoma and other solid cancers.
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000126257 650_7 $$2NLM Chemicals$$aAntigens, CD44
000126257 650_7 $$2NLM Chemicals$$aProto-Oncogene Proteins
000126257 650_7 $$2NLM Chemicals$$aRNA, Small Interfering
000126257 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor Protein-Tyrosine Kinases
000126257 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aaxl receptor tyrosine kinase
000126257 7001_ $$0P:(DE-He78)830be4979a39935ac6272eaebad5982a$$aPhillips, Emma$$b1$$udkfz
000126257 7001_ $$aKim, Sung-Hak$$b2
000126257 7001_ $$aTaylor, David$$b3
000126257 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, Thomas$$b4$$udkfz
000126257 7001_ $$0P:(DE-He78)39a8becd6fa9602e4871d18f3f6f8e09$$aPuccio, Laura$$b5$$udkfz
000126257 7001_ $$aHjelmeland, Anita B$$b6
000126257 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b7$$udkfz
000126257 7001_ $$aNakano, Ichiro$$b8
000126257 7001_ $$0P:(DE-HGF)0$$aGoidts, Violaine$$b9$$eLast author
000126257 773__ $$0PERI:(DE-600)2720528-9$$a10.1016/j.stemcr.2015.03.005$$gVol. 4, no. 5, p. 899 - 913$$n5$$p899 - 913$$tStem cell reports$$v4$$x2213-6711$$y2015
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