Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-3-16
pubmed:abstractText
Glioblastoma multiforme (GBM) is the most aggressive brain tumor that, by virtue of its resistance to chemotherapy and radiotherapy, is currently incurable. Identification of molecules whose targeting may eliminate GBM cells and/or sensitize glioblastoma cells to cytotoxic drugs is therefore urgently needed. CD44 is a major cell surface hyaluronan receptor and cancer stem cell marker that has been implicated in the progression of a variety of cancer types. However, the major downstream signaling pathways that mediate its protumor effects and the role of CD44 in the progression and chemoresponse of GBM have not been established. Here we show that CD44 is upregulated in GBM and that its depletion blocks GBM growth and sensitizes GBM cells to cytotoxic drugs in vivo. Consistent with this observation, CD44 antagonists potently inhibit glioma growth in preclinical mouse models. We provide the first evidence that CD44 functions upstream of the mammalian Hippo signaling pathway and that CD44 promotes tumor cell resistance to reactive oxygen species-induced and cytotoxic agent-induced stress by attenuating activation of the Hippo signaling pathway. Together, our results identify CD44 as a prime therapeutic target for GBM, establish potent antiglioma efficacy of CD44 antagonists, uncover a novel CD44 signaling pathway, and provide a first mechanistic explanation as to how upregulation of CD44 may constitute a key event in leading to cancer cell resistance to stresses of different origins. Finally, our results provide a rational explanation for the observation that functional inhibition of CD44 augments the efficacy of chemotherapy and radiation therapy.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-10037743, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-10652271, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-11170864, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-11316791, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-11390353, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-11423990, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-12177445, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-12464636, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-12511569, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-12511867, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-12697889, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-12894235, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-1500863, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-15229478, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-15746036, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-15827123, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-15882617, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16096061, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16204036, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16204178, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16341207, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16616334, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16751106, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16894141, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-16953231, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17097564, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17258190, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17442573, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17646864, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17882276, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17932492, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-17971532, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-18328423, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-18414046, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-18595010, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-18632626, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-18661343, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-18953558, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-19262113, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-19434087, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-19601881, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-7511044, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-7532176, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-8314845, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-9013673, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-9378774, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-9396767, http://linkedlifedata.com/resource/pubmed/commentcorrection/20197461-9887098
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2455-64
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
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