Rusyn, Lisa, Reinartz, Sebastian, Nikiforov, Anastasia, Mikhael, Nelly, vom Stein, Alexander, Kohlhas, Viktoria, Bloehdorn, Johannes ORCID: 0000-0003-1433-9702, Stilgenbauer, Stephan, Lohneis, Philipp, Buettner, Reinhard, Robrecht, Sandra, Fischer, Kirsten, Pallasch, Christian, Hallek, Michael ORCID: 0000-0002-7425-4455 and Seeger-Nukpezah, Tamina (2022). The scaffold protein NEDD9 is necessary for leukemia-cell migration and disease progression in a mouse model of chronic lymphocytic leukemia. Leukemia, 36 (7). S. 1794 - 1806. LONDON: SPRINGERNATURE. ISSN 1476-5551

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Abstract

The scaffold protein NEDD9 is frequently upregulated and hyperphosphorylated in cancers, and is associated with poor clinical outcome. NEDD9 promotes B-cell adhesion, migration and chemotaxis, pivotal processes for malignant development. We show that global or B-cell-specific deletion of Nedd9 in chronic lymphocytic leukemia (CLL) mouse models delayed CLL development, markedly reduced disease burden and resulted in significant survival benefit. NEDD9 was required for efficient CLL cell homing, chemotaxis, migration and adhesion. In CLL patients, peripheral NEDD9 expression was associated with adhesion and migration signatures as well as leukocyte count. Additionally, CLL lymph nodes frequently expressed high NEDD9 levels, with a subset of patients showing NEDD9 expression enriched in the CLL proliferation centers. Blocking activity of prominent NEDD9 effectors, including AURKA and HDAC6, effectively reduced CLL cell migration and chemotaxis. Collectively, our study provides evidence for a functional role of NEDD9 in CLL pathogenesis that involves intrinsic defects in adhesion, migration and homing.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rusyn, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinartz, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikiforov, AnastasiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mikhael, NellyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
vom Stein, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohlhas, ViktoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloehdorn, JohannesUNSPECIFIEDorcid.org/0000-0003-1433-9702UNSPECIFIED
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohneis, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robrecht, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, KirstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pallasch, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDorcid.org/0000-0002-7425-4455UNSPECIFIED
Seeger-Nukpezah, TaminaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-674289
DOI: 10.1038/s41375-022-01586-1
Journal or Publication Title: Leukemia
Volume: 36
Number: 7
Page Range: S. 1794 - 1806
Date: 2022
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 1476-5551
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ALPHA-4-BETA-1 INTEGRIN; CHEMOKINE RECEPTOR; SIGNALING PATHWAY; DOCKING PROTEIN; B-CELLS; MICROENVIRONMENT; VENETOCLAX; ACTIVATION; SUBSTRATE; PROLIFERATIONMultiple languages
Oncology; HematologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67428

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