RT Journal Article
SR Electronic
T1 Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900332
DO 10.26508/lsa.201900332
VO 4
IS 5
A1 Afanasyeva, Elena A
A1 Gartlgruber, Moritz
A1 Ryl, Tatsiana
A1 Decaesteker, Bieke
A1 Denecker, Geertrui
A1 Mönke, Gregor
A1 Toprak, Umut H
A1 Florez, Andres
A1 Torkov, Alica
A1 Dreidax, Daniel
A1 Herrmann, Carl
A1 Okonechnikov, Konstantin
A1 Ek, Sara
A1 Sharma, Ashwini Kumar
A1 Sagulenko, Vitaliya
A1 Speleman, Frank
A1 Henrich, Kai-Oliver
A1 Westermann, Frank
YR 2021
UL http://www.life-science-alliance.org/content/4/5/e201900332.abstract
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.