Matches in SemOpenAlex for { <https://semopenalex.org/work/W4324057319> ?p ?o ?g. }
- W4324057319 endingPage "5452" @default.
- W4324057319 startingPage "5452" @default.
- W4324057319 abstract "Heparan sulfate proteoglycans (HSPGs) possess various functions driving malignancy of tumors. However, their impact on tumor cell sensitivity to cytotoxic treatment is far less understood. Aiming to investigate this, we depleted HSPGs by downregulating Exostosin 1 (EXT1), a key enzyme in HS formation, or upregulating heparanase in human MV3 human melanoma cells, and investigated their response to cytotoxic drugs. Cytotoxicity of trametinib, doxorubicin, and mitoxantrone was detected by MTT assay. Insights into intracellular signaling was provided by kinome protein profiler array, and selected kinases were inhibited to investigate their impact on cell sensitization and migratory dynamics. EXT1 knockdown (EXT1kd) in MV3 cells affected the activity of doxorubicin and mitoxantrone, significantly increasing EC50 values two- or fourfold, respectively. Resistance formation was scarcely related to HSPG deficiency, suggested by enzymatic cleavage of HSPG in control cells. Notably, EXT1kd induced an upregulation of EGFR signaling via JNK and MEK/ERK, and hence blocking these kinases returned resistance to a sensitive level. JNK appeared as a key signal component, also inducing higher migratory activity of EXT1kd cells. Furthermore, EXT1kd upregulated thrombotic properties of MV3 cells, indicated by tissue factor and PAR-1 expression, functionally reflected by a stronger activation of platelet aggregation. EXT1 was confirmed to act as a tumor suppressor, shown here for the first time to affect chemosensitivity of melanoma cells." @default.
- W4324057319 created "2023-03-14" @default.
- W4324057319 creator A5005006760 @default.
- W4324057319 creator A5022422907 @default.
- W4324057319 creator A5031956896 @default.
- W4324057319 creator A5031991561 @default.
- W4324057319 creator A5065418938 @default.
- W4324057319 creator A5074301120 @default.
- W4324057319 date "2023-03-13" @default.
- W4324057319 modified "2023-09-25" @default.
- W4324057319 title "Exostosin 1 Knockdown Induces Chemoresistance in MV3 Melanoma Cells by Upregulating JNK and MEK/ERK Signaling" @default.
- W4324057319 cites W1577533565 @default.
- W4324057319 cites W1984853905 @default.
- W4324057319 cites W2011580649 @default.
- W4324057319 cites W2047649254 @default.
- W4324057319 cites W2059776541 @default.
- W4324057319 cites W2062110955 @default.
- W4324057319 cites W2064785827 @default.
- W4324057319 cites W2066616821 @default.
- W4324057319 cites W2068316985 @default.
- W4324057319 cites W2095373191 @default.
- W4324057319 cites W2108762252 @default.
- W4324057319 cites W2135692311 @default.
- W4324057319 cites W2155293713 @default.
- W4324057319 cites W2415671922 @default.
- W4324057319 cites W2689007723 @default.
- W4324057319 cites W2730862207 @default.
- W4324057319 cites W2742028015 @default.
- W4324057319 cites W2788244509 @default.
- W4324057319 cites W2793493731 @default.
- W4324057319 cites W2903765598 @default.
- W4324057319 cites W2937369800 @default.
- W4324057319 cites W2970311879 @default.
- W4324057319 cites W2990492054 @default.
- W4324057319 cites W3002978601 @default.
- W4324057319 cites W3008818246 @default.
- W4324057319 cites W3014913757 @default.
- W4324057319 cites W3017730150 @default.
- W4324057319 cites W3025027860 @default.
- W4324057319 cites W3048072144 @default.
- W4324057319 cites W3084054647 @default.
- W4324057319 cites W3091977395 @default.
- W4324057319 cites W3138797151 @default.
- W4324057319 cites W3149005467 @default.
- W4324057319 cites W3171021092 @default.
- W4324057319 cites W3214208097 @default.
- W4324057319 cites W4210737816 @default.
- W4324057319 cites W4225571410 @default.
- W4324057319 cites W4251090080 @default.
- W4324057319 cites W4281648733 @default.
- W4324057319 cites W4283364393 @default.
- W4324057319 cites W4310569537 @default.
- W4324057319 cites W4310941456 @default.
- W4324057319 doi "https://doi.org/10.3390/ijms24065452" @default.
- W4324057319 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36982528" @default.
- W4324057319 hasPublicationYear "2023" @default.
- W4324057319 type Work @default.
- W4324057319 citedByCount "1" @default.
- W4324057319 countsByYear W43240573192023 @default.
- W4324057319 crossrefType "journal-article" @default.
- W4324057319 hasAuthorship W4324057319A5005006760 @default.
- W4324057319 hasAuthorship W4324057319A5022422907 @default.
- W4324057319 hasAuthorship W4324057319A5031956896 @default.
- W4324057319 hasAuthorship W4324057319A5031991561 @default.
- W4324057319 hasAuthorship W4324057319A5065418938 @default.
- W4324057319 hasAuthorship W4324057319A5074301120 @default.
- W4324057319 hasBestOaLocation W43240573191 @default.
- W4324057319 hasConcept C104317684 @default.
- W4324057319 hasConcept C109316439 @default.
- W4324057319 hasConcept C127561419 @default.
- W4324057319 hasConcept C154317977 @default.
- W4324057319 hasConcept C173396325 @default.
- W4324057319 hasConcept C184235292 @default.
- W4324057319 hasConcept C185592680 @default.
- W4324057319 hasConcept C190283241 @default.
- W4324057319 hasConcept C202751555 @default.
- W4324057319 hasConcept C2776694085 @default.
- W4324057319 hasConcept C2781303535 @default.
- W4324057319 hasConcept C502942594 @default.
- W4324057319 hasConcept C54355233 @default.
- W4324057319 hasConcept C55493867 @default.
- W4324057319 hasConcept C57074206 @default.
- W4324057319 hasConcept C62478195 @default.
- W4324057319 hasConcept C86803240 @default.
- W4324057319 hasConcept C95444343 @default.
- W4324057319 hasConceptScore W4324057319C104317684 @default.
- W4324057319 hasConceptScore W4324057319C109316439 @default.
- W4324057319 hasConceptScore W4324057319C127561419 @default.
- W4324057319 hasConceptScore W4324057319C154317977 @default.
- W4324057319 hasConceptScore W4324057319C173396325 @default.
- W4324057319 hasConceptScore W4324057319C184235292 @default.
- W4324057319 hasConceptScore W4324057319C185592680 @default.
- W4324057319 hasConceptScore W4324057319C190283241 @default.
- W4324057319 hasConceptScore W4324057319C202751555 @default.
- W4324057319 hasConceptScore W4324057319C2776694085 @default.
- W4324057319 hasConceptScore W4324057319C2781303535 @default.
- W4324057319 hasConceptScore W4324057319C502942594 @default.
- W4324057319 hasConceptScore W4324057319C54355233 @default.