Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma

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

doi:10.26508/lsa.201900332

Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma

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

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	Life Science Alliance
Volume	4
Issue number	5
DOIs	https://doi.org/10.26508/lsa.201900332
Publication status	Published - 2021

Subject classification (UKÄ)

Cancer and Oncology
Cell and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.26508/lsa.201900332

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Afanasyeva, E. A., Gartlgruber, M., Ryl, T., Decaesteker, B., Denecker, G., Mönke, G., Toprak, U. H., Florez, A., Torkov, A., Dreidax, D., Herrmann, C., Okonechnikov, K., Ek, S., Sharma, A. K., Sagulenko, V., Speleman, F., Henrich, K. O., & Westermann, F. (2021). Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma. Life Science Alliance, 4(5). https://doi.org/10.26508/lsa.201900332

@article{196c5d1ea35e4f7caf3dede6ac50b6ad,

title = "Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma",

abstract = "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.",

author = "Afanasyeva, {Elena A.} and Moritz Gartlgruber and Tatsiana Ryl and Bieke Decaesteker and Geertrui Denecker and Gregor M{\"o}nke and Toprak, {Umut H.} and Andres Florez and Alica Torkov and Daniel Dreidax and Carl Herrmann and Konstantin Okonechnikov and Sara Ek and Sharma, {Ashwini Kumar} and Vitaliya Sagulenko and Frank Speleman and Henrich, {Kai Oliver} and Frank Westermann",

year = "2021",

doi = "10.26508/lsa.201900332",

language = "English",

volume = "4",

journal = "Life Science Alliance",

issn = "2575-1077",

publisher = "Rockefeller University Press",

number = "5",

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Afanasyeva, EA, Gartlgruber, M, Ryl, T, Decaesteker, B, Denecker, G, Mönke, G, Toprak, UH, Florez, A, Torkov, A, Dreidax, D, Herrmann, C, Okonechnikov, K, Ek, S, Sharma, AK, Sagulenko, V, Speleman, F, Henrich, KO & Westermann, F 2021, 'Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma', Life Science Alliance, vol. 4, no. 5. https://doi.org/10.26508/lsa.201900332

TY - JOUR

T1 - Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma

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

PY - 2021

Y1 - 2021

N2 - 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.

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.

U2 - 10.26508/lsa.201900332

DO - 10.26508/lsa.201900332

M3 - Article

C2 - 33658318

AN - SCOPUS:85102483206

SN - 2575-1077

VL - 4

JO - Life Science Alliance

JF - Life Science Alliance

IS - 5

ER -

Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma

Abstract

Subject classification (UKÄ)

UN SDGs

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