Titre
A Cluster of Evolutionarily Recent KRAB Zinc Finger Proteins Protects Cancer Cells from Replicative Stress-Induced Inflammation.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Martins, F.
Auteure/Auteur
Rosspopoff, O.
Auteure/Auteur
Carlevaro-Fita, J.
Auteure/Auteur
Forey, R.
Auteure/Auteur
Offner, S.
Auteure/Auteur
Planet, E.
Auteure/Auteur
Pulver, C.
Auteure/Auteur
Pak, H.
Auteure/Auteur
Huber, F.
Auteure/Auteur
Michaux, J.
Auteure/Auteur
Bassani-Sternberg, M.
Auteure/Auteur
Turelli, P.
Auteure/Auteur
Trono, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1538-7445
Statut éditorial
Publié
Date de publication
2024-03-15
Volume
84
Numéro
6
Première page
808
Dernière page/numéro d’article
826
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress leads to mitotic catastrophe and inflammatory responses that promote immune rejection. KRAB domain-containing zinc finger proteins (KZFP) contribute to heterochromatin maintenance at transposable elements (TE). Here, we identified an association of upregulation of a cluster of primate-specific KZFPs with poor prognosis, increased copy-number alterations, and changes in the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL). Depleting two of these KZFPs targeting evolutionarily recent TEs, ZNF587 and ZNF417, impaired the proliferation of cells derived from DLBCL and several other tumor types. ZNF587 and ZNF417 depletion led to heterochromatin redistribution, replicative stress, and cGAS-STING-mediated induction of an interferon/inflammatory response, which enhanced susceptibility to macrophage-mediated phagocytosis and increased surface expression of HLA-I, together with presentation of a neoimmunopeptidome. Thus, cancer cells can exploit KZFPs to dampen TE-originating surveillance mechanisms, which likely facilitates clonal expansion, diversification, and immune evasion.
Upregulation of a cluster of primate-specific KRAB zinc finger proteins in cancer cells prevents replicative stress and inflammation by regulating heterochromatin maintenance, which could facilitate the development of improved biomarkers and treatments.
Upregulation of a cluster of primate-specific KRAB zinc finger proteins in cancer cells prevents replicative stress and inflammation by regulating heterochromatin maintenance, which could facilitate the development of improved biomarkers and treatments.
PID Serval
serval:BIB_26A70ECA1060
PMID
Open Access
Oui
Date de création
2024-02-15T15:24:35.390Z
Date de création dans IRIS
2025-05-20T16:25:51Z
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Nom
38345497_BIB_26A70ECA1060.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
10.56 MB
Format
Adobe PDF
PID Serval
serval:BIB_26A70ECA1060.P001
URN
urn:nbn:ch:serval-BIB_26A70ECA10606
Somme de contrôle
(MD5):8ae23f5df692c1ab09fb930047046ba0