Matches in SemOpenAlex for { <https://semopenalex.org/work/W2981588353> ?p ?o ?g. }
- W2981588353 endingPage "78" @default.
- W2981588353 startingPage "69" @default.
- W2981588353 abstract "Abstract The aggressive brain tumor glioblastoma (GBM) is characterized by rapid cellular infiltration of brain tissue, raising the possibility that disease progression could potentially be slowed by disrupting the machinery of cell migration. The LIM kinase isoforms LIMK1 and LIMK2 (LIMK1/2) play important roles in cell polarization, migration, and invasion and are markedly upregulated in GBM and many other infiltrative cancers. Yet, it remains unclear whether LIMK suppression could serve as a viable basis for combating GBM infiltration. In this study, we investigated effects of LIMK1/2 suppression on GBM invasion by combining GBM culture models, engineered invasion paradigms, and mouse xenograft models. While knockdown of either LIMK1 or LIMK2 only minimally influenced invasion in culture, simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells (TIC) in both Boyden chamber and 3D hyaluronic acid spheroid invasion assays. Furthermore, LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis. In an orthotopic xenograft model, TICs stably transduced with LIMK1/2 shRNA were implanted intracranially in immunocompromised mice. Tumors derived from LIMK1/2 knockdown TICs were substantially smaller and showed delayed growth kinetics and more distinct margins than tumors derived from control TICs. Overall, LIMK1/2 suppression increased mean survival time by 30%. These findings indicate that LIMK1/2 strongly regulate GBM invasive motility and tumor progression and support further exploration of LIMK1/2 as druggable targets. Significance: Targeting the actin-binding proteins LIMK1 and LIMK2 significantly diminishes glioblastoma invasion and spread, suggesting the potential value of these proteins as therapeutic targets." @default.
- W2981588353 created "2019-11-01" @default.
- W2981588353 creator A5030506364 @default.
- W2981588353 creator A5043931957 @default.
- W2981588353 creator A5048305189 @default.
- W2981588353 creator A5051162336 @default.
- W2981588353 creator A5063938919 @default.
- W2981588353 creator A5076751296 @default.
- W2981588353 creator A5088021700 @default.
- W2981588353 date "2020-01-01" @default.
- W2981588353 modified "2023-10-14" @default.
- W2981588353 title "Suppression of LIM Kinase 1 and LIM Kinase 2 Limits Glioblastoma Invasion" @default.
- W2981588353 cites W1540639874 @default.
- W2981588353 cites W1880022530 @default.
- W2981588353 cites W1933768295 @default.
- W2981588353 cites W1966501485 @default.
- W2981588353 cites W1967518676 @default.
- W2981588353 cites W1969905245 @default.
- W2981588353 cites W1978312684 @default.
- W2981588353 cites W1979988883 @default.
- W2981588353 cites W1984483719 @default.
- W2981588353 cites W1989752993 @default.
- W2981588353 cites W1990367597 @default.
- W2981588353 cites W1993695768 @default.
- W2981588353 cites W1995757732 @default.
- W2981588353 cites W1997903864 @default.
- W2981588353 cites W1999011283 @default.
- W2981588353 cites W2001419152 @default.
- W2981588353 cites W2003173961 @default.
- W2981588353 cites W2008177298 @default.
- W2981588353 cites W2018671779 @default.
- W2981588353 cites W2029728492 @default.
- W2981588353 cites W2030582971 @default.
- W2981588353 cites W2039233803 @default.
- W2981588353 cites W2049132016 @default.
- W2981588353 cites W2064347745 @default.
- W2981588353 cites W2074812494 @default.
- W2981588353 cites W2077484148 @default.
- W2981588353 cites W2089340935 @default.
- W2981588353 cites W2109816625 @default.
- W2981588353 cites W2111838337 @default.
- W2981588353 cites W2114843025 @default.
- W2981588353 cites W2122693202 @default.
- W2981588353 cites W2125356859 @default.
- W2981588353 cites W2128683756 @default.
- W2981588353 cites W2131554707 @default.
- W2981588353 cites W2134807618 @default.
- W2981588353 cites W2134951427 @default.
- W2981588353 cites W2135174117 @default.
- W2981588353 cites W2140088548 @default.
- W2981588353 cites W2140614835 @default.
- W2981588353 cites W2142381684 @default.
- W2981588353 cites W2143519804 @default.
- W2981588353 cites W2144438046 @default.
- W2981588353 cites W2149441684 @default.
- W2981588353 cites W2149630056 @default.
- W2981588353 cites W2151801027 @default.
- W2981588353 cites W2157714833 @default.
- W2981588353 cites W2165886816 @default.
- W2981588353 cites W2168979411 @default.
- W2981588353 cites W2305154056 @default.
- W2981588353 cites W2339584655 @default.
- W2981588353 cites W2399755425 @default.
- W2981588353 cites W2408360093 @default.
- W2981588353 cites W2526011086 @default.
- W2981588353 cites W2600812848 @default.
- W2981588353 cites W2604317589 @default.
- W2981588353 cites W2616386153 @default.
- W2981588353 cites W2730651489 @default.
- W2981588353 cites W2760276067 @default.
- W2981588353 cites W2766471903 @default.
- W2981588353 cites W2779222211 @default.
- W2981588353 cites W2806160889 @default.
- W2981588353 cites W2885875354 @default.
- W2981588353 cites W2950347823 @default.
- W2981588353 cites W2967167596 @default.
- W2981588353 doi "https://doi.org/10.1158/0008-5472.can-19-1237" @default.
- W2981588353 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6942638" @default.
- W2981588353 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31641031" @default.
- W2981588353 hasPublicationYear "2020" @default.
- W2981588353 type Work @default.
- W2981588353 sameAs 2981588353 @default.
- W2981588353 citedByCount "16" @default.
- W2981588353 countsByYear W29815883532020 @default.
- W2981588353 countsByYear W29815883532021 @default.
- W2981588353 countsByYear W29815883532022 @default.
- W2981588353 countsByYear W29815883532023 @default.
- W2981588353 crossrefType "journal-article" @default.
- W2981588353 hasAuthorship W2981588353A5030506364 @default.
- W2981588353 hasAuthorship W2981588353A5043931957 @default.
- W2981588353 hasAuthorship W2981588353A5048305189 @default.
- W2981588353 hasAuthorship W2981588353A5051162336 @default.
- W2981588353 hasAuthorship W2981588353A5063938919 @default.
- W2981588353 hasAuthorship W2981588353A5076751296 @default.
- W2981588353 hasAuthorship W2981588353A5088021700 @default.
- W2981588353 hasBestOaLocation W29815883531 @default.
- W2981588353 hasConcept C137738243 @default.
- W2981588353 hasConcept C170493617 @default.