Immunoglobulin superfamily member 8 maintains myeloid leukemia stem cells through inhibition of β-catenin degradation.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
03
11
2021
accepted:
30
03
2022
revised:
09
03
2022
pubmed:
15
4
2022
medline:
7
6
2022
entrez:
14
4
2022
Statut:
ppublish
Résumé
The identification of characteristic differences between cancer stem cells and their normal counterparts remains a key challenge for cancer treatment. Here, we investigated the role of immunoglobulin superfamily member 8 (Igsf8, also known as EWI-2, PGRL, and CD316) on normal and malignant hematopoietic stem cells, mainly using the conditional knockout model. Deletion of Igsf8 did not affect steady state hematopoiesis, but it led to a significant improvement of survival in mouse myeloid leukemia models. Deletion of Igsf8 significantly depletes leukemia stem cells (LSCs) through enhanced apoptosis and β-catenin degradation. At a molecular level, we found that activation of β-catenin in LSCs depends on Igsf8, which promotes the association of FZD4 with its co-receptor LRP6 in the presence of Igsf8. Similarly, IGSF8 inhibition blocks the colony-forming ability of LSCs and improves the survival of recipients in xenograft models of myeloid leukemia. Collectively, these data indicate strong genetic evidence identifying Igsf8 as a key regulator of myeloid leukemia and the possibility that targeting IGSF8 may serve as a new therapeutic approach against myeloid leukemia.
Identifiants
pubmed: 35418614
doi: 10.1038/s41375-022-01564-7
pii: 10.1038/s41375-022-01564-7
doi:
Substances chimiques
CTNNB1 protein, mouse
0
Carrier Proteins
0
FZD4 protein, human
0
Frizzled Receptors
0
IgSF8 protein, mouse
0
Immunoglobulins
0
Membrane Proteins
0
Transcription Factors
0
beta Catenin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1550-1562Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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