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Kalirin-RAC control...
Kalirin-RAC controls nucleokinetic migration in ADRN-type neuroblastoma
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- Afanasyeva, Elena A. (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Gartlgruber, Moritz (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Ryl, Tatsiana (author)
- University of Duisburg-Essen
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- Decaesteker, Bieke (author)
- Ghent University
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- Denecker, Geertrui (author)
- Ghent University
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- Mönke, Gregor (author)
- European Molecular Biology Laboratory Heidelberg
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- Toprak, Umut H. (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Florez, Andres (author)
- Harvard University,Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Torkov, Alica (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Dreidax, Daniel (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Herrmann, Carl (author)
- German Cancer Research Centre
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- Okonechnikov, Konstantin (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Ek, Sara (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Sharma, Ashwini Kumar (author)
- Heidelberg University,German Cancer Research Centre
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- Sagulenko, Vitaliya (author)
- University of Queensland
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- Speleman, Frank (author)
- Ghent University
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- Henrich, Kai Oliver (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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- Westermann, Frank (author)
- Hopp Children’s Cancer Center Heidelberg (KiTZ)
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(creator_code:org_t)
- 2021-03-03
- 2021
- English.
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In: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 4:5
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- By the author/editor
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Afanasyeva, Elen ...
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Gartlgruber, Mor ...
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Ryl, Tatsiana
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Decaesteker, Bie ...
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Denecker, Geertr ...
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Mönke, Gregor
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show more...
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Toprak, Umut H.
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Florez, Andres
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Torkov, Alica
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Dreidax, Daniel
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Herrmann, Carl
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Okonechnikov, Ko ...
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Ek, Sara
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Sharma, Ashwini ...
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Sagulenko, Vital ...
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Speleman, Frank
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Henrich, Kai Oli ...
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Westermann, Fran ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Life Science All ...
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Lund University