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Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma

Afanasyeva, Elena A. ; Gartlgruber, Moritz ; Ryl, Tatsiana ; Decaesteker, Bieke ; Denecker, Geertrui ; Mönke, Gregor ; Toprak, Umut H. ; Florez, Andres ; Torkov, Alica and Dreidax, Daniel , et al. (2021) In Life Science Alliance 4(5).
Abstract

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... (More)

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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type
Contribution to journal
publication status
published
subject
in
Life Science Alliance
volume
4
issue
5
publisher
Rockefeller University Press
external identifiers
  • scopus:85102483206
  • pmid:33658318
ISSN
2575-1077
DOI
10.26508/lsa.201900332
language
English
LU publication?
yes
id
196c5d1e-a35e-4f7c-af3d-ede6ac50b6ad
date added to LUP
2021-03-24 08:38:14
date last changed
2024-04-18 04:04:52
@article{196c5d1e-a35e-4f7c-af3d-ede6ac50b6ad,
  abstract     = {{<p>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.</p>}},
  author       = {{Afanasyeva, Elena A. and Gartlgruber, Moritz and Ryl, Tatsiana and Decaesteker, Bieke and Denecker, Geertrui and Mönke, Gregor and Toprak, Umut H. and Florez, Andres and Torkov, Alica and Dreidax, Daniel and Herrmann, Carl and Okonechnikov, Konstantin and Ek, Sara and Sharma, Ashwini Kumar and Sagulenko, Vitaliya and Speleman, Frank and Henrich, Kai Oliver and Westermann, Frank}},
  issn         = {{2575-1077}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Life Science Alliance}},
  title        = {{Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma}},
  url          = {{http://dx.doi.org/10.26508/lsa.201900332}},
  doi          = {{10.26508/lsa.201900332}},
  volume       = {{4}},
  year         = {{2021}},
}