Autocrine LTA signaling drives NF-κB and JAK-STAT activity and myeloid gene expression in Hodgkin lymphoma.


Journal

Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509

Informations de publication

Date de publication:
28 03 2019
Historique:
received: 22 08 2018
accepted: 22 01 2019
pubmed: 31 1 2019
medline: 4 12 2019
entrez: 31 1 2019
Statut: ppublish

Résumé

Persistent NF-κB activation is a hallmark of the malignant Hodgkin/Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL). Genomic lesions, Epstein-Barr virus infection, soluble factors, and tumor-microenvironment interactions contribute to this activation. Here, in an unbiased approach to identify the cHL cell-secreted key factors for NF-κB activation, we have dissected the secretome of cultured cHL cells by chromatography and subsequent mass spectrometry. We identified lymphotoxin-α (LTA) as the causative factor for autocrine and paracrine activation of canonical and noncanonical NF-κB in cHL cell lines. In addition to inducing NF-κB, LTA promotes JAK2/STAT6 signaling.

Identifiants

pubmed: 30696620
pii: S0006-4971(20)42671-0
doi: 10.1182/blood-2018-08-871293
doi:

Substances chimiques

Lymphotoxin-alpha 0
NF-kappa B 0
STAT6 Transcription Factor 0
STAT6 protein, human 0
JAK2 protein, human EC 2.7.10.2
Janus Kinase 2 EC 2.7.10.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1489-1494

Informations de copyright

© 2019 by The American Society of Hematology.

Auteurs

Linda von Hoff (L)

Research Group "Signal Transduction in Tumor Cells,".

Eva Kärgel (E)

Research Group "Signal Transduction in Tumor Cells,".

Vedran Franke (V)

Research Group "Bioinformatics/Mathematical Modelling Platform,".

Erik McShane (E)

Research Group "Proteome Dynamics,".

Kathrin W Schulz-Beiss (KW)

Research Group "Structural Biology of Membrane Associated Processes,".

Giannino Patone (G)

Research Group "Genetics and Genomics of Cardiovascular Diseases," and.

Nikolai Schleussner (N)

Research Group "Biology of Malignant Lymphomas," Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; and.
Research Group "Hematology, Oncology, and Tumor Immunology," Charité-Universitätsmedizin Berlin, Berlin, Germany.

Marina Kolesnichenko (M)

Research Group "Signal Transduction in Tumor Cells,".

Norbert Hübner (N)

Research Group "Genetics and Genomics of Cardiovascular Diseases," and.

Oliver Daumke (O)

Research Group "Structural Biology of Membrane Associated Processes,".

Matthias Selbach (M)

Research Group "Proteome Dynamics,".

Altuna Akalin (A)

Research Group "Bioinformatics/Mathematical Modelling Platform,".

Stephan Mathas (S)

Research Group "Biology of Malignant Lymphomas," Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; and.
Research Group "Hematology, Oncology, and Tumor Immunology," Charité-Universitätsmedizin Berlin, Berlin, Germany.

Claus Scheidereit (C)

Research Group "Signal Transduction in Tumor Cells,".

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Classifications MeSH