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Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma

The migrational propensity of neuroblastoma is affected by cell identity, but the mechanisms behind the divergence remain unknown. Using RNAi and time-lapse imaging, we show that ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration that relies on several integral comp...

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Hauptverfasser: Afanasyeva, Elena (VerfasserIn) , Gartlgruber, Moritz (VerfasserIn) , Ryl, Tatsiana (VerfasserIn) , Decaesteker, Bieke (VerfasserIn) , Denecker, Geertrui (VerfasserIn) , Mönke, Gregor (VerfasserIn) , Toprak, Umut (VerfasserIn) , Flórez, Andrés (VerfasserIn) , Torkov, Alica (VerfasserIn) , Dreidax, Daniel (VerfasserIn) , Herrmann, Carl (VerfasserIn) , Okonechnikov, Konstantin (VerfasserIn) , Ek, Sara (VerfasserIn) , Sharma, Ashwini Kumar (VerfasserIn) , Sagulenko, Vitaliya (VerfasserIn) , Speleman, Frank (VerfasserIn) , Henrich, Kai-Oliver (VerfasserIn) , Westermann, Frank (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 3 March, 2021
In: Life science alliance
Year: 2021, Jahrgang: 4, Heft: 5, Pages: 1-25
ISSN:2575-1077
DOI:10.26508/lsa.201900332
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.26508/lsa.201900332
Verlag, lizenzpflichtig, Volltext: https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=DynamicDOIArticle&SrcApp=WOS&KeyAID=10.26508%2Flsa.201900332&DestApp=DOI&SrcAppSID=F5ufCNacAlsOyhPlCuO&SrcJTitle=LIFE+SCIENCE+ALLIANCE&DestDOIRegistrantName=Life+Science+Alliance
Volltext
Verfasserangaben:Elena A Afanasyeva, Moritz Gartlgruber, Tatsiana Ryl, Bieke Decaesteker, Geertrui Denecker, Gregor Moenke, Umut H Toprak, Andres Florez, Alica Torkov, Daniel Dreidax, Carl Herrmann, Konstantin Okonechnikov, Sara Ek, Ashwini Kumar Sharma, Vitaliya Sagulenko, Frank Speleman, Kai-Oliver Henrich, Frank Westermann
Beschreibung
Zusammenfassung:The migrational propensity of neuroblastoma is affected by cell identity, but the mechanisms behind the divergence remain unknown. Using RNAi and time-lapse imaging, we show that ADRN-type NB cells exhibit RAC1- and kalirin-dependent nucleokinetic (NUC) migration that relies on several integral components of neuronal migration. Inhibition of NUC migration by RAC1 and kalirin-GEF1 inhibitors occurs without hampering cell proliferation and ADRN identity. Using three clinically relevant expression dichotomies, we reveal that most of up-regulated mRNAs in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells are associated with low-risk characteristics. The computational analysis shows that, in a context of overall gene set poverty, the upregulomes in RAC1- and kalirin-GEF1-suppressed ADRN-type cells are a batch of AU-rich element-containing mRNAs, which suggests a link between NUC migration and mRNA stability. Gene set enrichment analysis-based search for vulnerabilities reveals prospective weak points in RAC1- and kalirin-GEF1-suppressed ADRN-type NB cells, including activities of H3K27- and DNA methyltransferases. Altogether, these data support the introduction of NUC inhibitors into cancer treatment research.
Beschreibung:Gesehen am 19.08.2021
Beschreibung:Online Resource
ISSN:2575-1077
DOI:10.26508/lsa.201900332

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