PT  - JOURNAL ARTICLE
AU  - Afanasyeva, Elena A
AU  - Gartlgruber, Moritz
AU  - Ryl, Tatsiana
AU  - Decaesteker, Bieke
AU  - Denecker, Geertrui
AU  - Mönke, Gregor
AU  - Toprak, Umut H
AU  - Florez, Andres
AU  - Torkov, Alica
AU  - Dreidax, Daniel
AU  - Herrmann, Carl
AU  - Okonechnikov, Konstantin
AU  - Ek, Sara
AU  - Sharma, Ashwini Kumar
AU  - Sagulenko, Vitaliya
AU  - Speleman, Frank
AU  - Henrich, Kai-Oliver
AU  - Westermann, Frank
TI  - Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma
AID  - 10.26508/lsa.201900332
DP  - 2021 May 01
TA  - Life Science Alliance
PG  - e201900332
VI  - 4
IP  - 5
4099  - http://www.life-science-alliance.org/content/4/5/e201900332.short
4100  - http://www.life-science-alliance.org/content/4/5/e201900332.full
SO  - Life Sci. Alliance2021 May 01; 4
AB  - 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.