%0 Journal Article %A Elena A Afanasyeva %A Moritz Gartlgruber %A Tatsiana Ryl %A Bieke Decaesteker %A Geertrui Denecker %A Gregor Mönke %A Umut H Toprak %A Andres Florez %A Alica Torkov %A Daniel Dreidax %A Carl Herrmann %A Konstantin Okonechnikov %A Sara Ek %A Ashwini Kumar Sharma %A Vitaliya Sagulenko %A Frank Speleman %A Kai-Oliver Henrich %A Frank Westermann %T Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma %D 2021 %R 10.26508/lsa.201900332 %J Life Science Alliance %P e201900332 %V 4 %N 5 %X 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. %U https://www.life-science-alliance.org/content/lsa/4/5/e201900332.full.pdf