Downregulation of stromal syntenin sustains AML development.
cell-to-cell communication
syntenin
tumor aggressiveness
tumor-stroma
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
08 11 2023
08 11 2023
Historique:
revised:
13
09
2023
received:
15
02
2023
accepted:
14
09
2023
medline:
9
11
2023
pubmed:
11
10
2023
entrez:
11
10
2023
Statut:
ppublish
Résumé
The crosstalk between cancer and stromal cells plays a critical role in tumor progression. Syntenin is a small scaffold protein involved in the regulation of intercellular communication that is emerging as a target for cancer therapy. Here, we show that certain aggressive forms of acute myeloid leukemia (AML) reduce the expression of syntenin in bone marrow stromal cells (BMSC). Stromal syntenin deficiency, in turn, generates a pro-tumoral microenvironment. From serial transplantations in mice and co-culture experiments, we conclude that syntenin-deficient BMSC stimulate AML aggressiveness by promoting AML cell survival and protein synthesis. This pro-tumoral activity is supported by increased expression of endoglin, a classical marker of BMSC, which in trans stimulates AML translational activity. In short, our study reveals a vicious signaling loop potentially at the heart of AML-stroma crosstalk and unsuspected tumor-suppressive effects of syntenin that need to be considered during systemic targeting of syntenin in cancer therapy.
Identifiants
pubmed: 37819151
doi: 10.15252/emmm.202317570
pmc: PMC10630886
doi:
Substances chimiques
Syntenins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e17570Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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