Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma
© 2021 Afanasyeva et al..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
Life science alliance - 4(2021), 5 vom: 09. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Afanasyeva, Elena A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.10.2021 Date Revised 31.03.2024 published: Electronic-Print GENBANK: NM_003947 Citation Status MEDLINE |
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| doi: |
10.26508/lsa.201900332 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2021 Afanasyeva et al. | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Mönke, Gregor |e verfasserin |4 aut | |
| 700 | 1 | |a Toprak, Umut H |e verfasserin |4 aut | |
| 700 | 1 | |a Florez, Andres |e verfasserin |4 aut | |
| 700 | 1 | |a Torkov, Alica |e verfasserin |4 aut | |
| 700 | 1 | |a Dreidax, Daniel |e verfasserin |4 aut | |
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| 700 | 1 | |a Okonechnikov, Konstantin |e verfasserin |4 aut | |
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