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 Elena A Afanasyeva
A1 Moritz Gartlgruber
A1 Tatsiana Ryl
A1 Bieke Decaesteker
A1 Geertrui Denecker
A1 Gregor Mönke
A1 Umut H Toprak
A1 Andres Florez
A1 Alica Torkov
A1 Daniel Dreidax
A1 Carl Herrmann
A1 Konstantin Okonechnikov
A1 Sara Ek
A1 Ashwini Kumar Sharma
A1 Vitaliya Sagulenko
A1 Frank Speleman
A1 Kai-Oliver Henrich
A1 Frank Westermann
YR 2021
UL https://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.