Targeting metastasis-initiating cancer stem cells in gastric cancer with leukaemia inhibitory factor.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
07 Mar 2024
07 Mar 2024
Historique:
received:
21
04
2023
accepted:
31
01
2024
revised:
30
01
2024
medline:
8
3
2024
pubmed:
8
3
2024
entrez:
7
3
2024
Statut:
epublish
Résumé
Gastric cancer's (GC) bad prognosis is usually associated with metastatic spread. Invasive cancer stem cells (CSC) are considered to be the seed of GC metastasis and not all CSCs are able to initiate metastasis. Targeting these aggressive metastasis-initiating CSC (MIC) is thus vital. Leukaemia inhibitory factor (LIF) is hereby used to target Hippo pathway oncogenic members, found to be induced in GC and associated with CSC features. LIF-treated GC cell lines, patient-derived xenograft (PDX) cells and/or CSC tumourspheres underwent transcriptomics, laser microdissection-associated proteomics, 2D and 3D invasion assays and in vivo xenograft in mice blood circulation. LIFR expression was analysed on tissue microarrays from GC patients and in silico from public databases. LIF-treated cells, especially CSC, presented decreased epithelial to mesenchymal transition (EMT) phenotype and invasion capacity in vitro, and lower metastasis initiation ability in vivo. These effects involved both the Hippo and Jak/Stat pathways. Finally, GC's high LIFR expression was associated with better clinical outcomes in patients. LIF treatment could thus represent a targeted anti-CSC strategy to fight against metastatic GC, and LIFR detection in primary tumours could constitute a potential new prognosis marker in this disease.
Identifiants
pubmed: 38453889
doi: 10.1038/s41420-024-01839-1
pii: 10.1038/s41420-024-01839-1
doi:
Types de publication
Journal Article
Langues
eng
Pagination
120Informations de copyright
© 2024. The Author(s).
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