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.