Abstract：
:Glioblastoma multiforme (GBMs) are recurrent lethal brain tumours. Recurrent GBMs often exhibit mesenchymal, stem-like phenotypes that could explain their resistance to therapy. Analyses revealed that recurrent GBMs have increased tension and express high levels of glycoproteins that increase the bulkiness of the glycocalyx. Studies showed that a bulky glycocalyx potentiates integrin mechanosignalling and tissue tension and promotes a mesenchymal, stem-like phenotype in GBMs. Gain- and loss-of-function studies implicated integrin mechanosignalling as an inducer of GBM growth, survival, invasion and treatment resistance, and a mesenchymal, stem-like phenotype. Mesenchymal-like GBMs were highly contractile and expressed elevated levels of glycoproteins that expanded their glycocalyx, and they were surrounded by a stiff extracellular matrix that potentiated integrin mechanosignalling. Our findings suggest that there is a dynamic and reciprocal link between integrin mechanosignalling and a bulky glycocalyx, implying a causal link towards a mesenchymal, stem-like phenotype in GBMs. Strategies to ameliorate GBM tissue tension offer a therapeutic approach to reduce mortality due to GBM.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Barnes JM,Kaushik S,Bainer RO,Sa JK,Woods EC,Kai F,Przybyla L,Lee M,Lee HW,Tung JC,Maller O,Barrett AS,Lu KV,Lakins JN,Hansen KC,Obernier K,Alvarez-Buylla A,Bergers G,Phillips JJ,Nam DH,Bertozzi CR,Weaver VMdoi
10.1038/s41556-018-0183-3subject
Has Abstractpub_date
2018-10-01 00:00:00pages
1203-1214issue
10eissn
1465-7392issn
1476-4679pii
10.1038/s41556-018-0183-3journal_volume
20pub_type
杂志文章abstract：:Coordination of microtubules and the actin cytoskeleton is important in several types of cell movement. mDia1 is a member of the formin-homology family of proteins and an effector of the small GTPase Rho. It contains the Rho-binding domain in its amino terminus and two distinct regions of formin homology, FH1 in the m...
journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2001-01-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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更新日期：2007-12-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35070050
更新日期：2001-04-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1517
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更新日期：2010-07-01 00:00:00
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更新日期：2013-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/ncb1341
更新日期：2006-01-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1731
更新日期：2008-06-01 00:00:00
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doi：10.1038/35019537
更新日期：2000-08-01 00:00:00
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journal_title：Nature cell biology
pub_type： 杂志文章,评审
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更新日期：2014-10-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2011-11-02 00:00:00
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更新日期：2010-09-01 00:00:00
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pub_type： 已发布勘误
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journal_title：Nature cell biology
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