Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells.
Neoplastic Stem Cells
/ metabolism
Humans
Drug Resistance, Neoplasm
/ drug effects
Fatty Acids
/ metabolism
Pancreatic Neoplasms
/ pathology
Oxidation-Reduction
Cell Line, Tumor
Carcinogenesis
/ pathology
Animals
Oxidative Phosphorylation
/ drug effects
Cell Self Renewal
/ drug effects
Lipid Metabolism
/ drug effects
AC133 Antigen
/ metabolism
Mice
Gene Expression Regulation, Neoplastic
Cancer stem cells
Chemoresistance
Fatty acid
Lipid metabolism
Oxidative phosphorylation
Pancreatic cancer
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
28 Aug 2024
28 Aug 2024
Historique:
received:
24
04
2024
accepted:
11
08
2024
medline:
31
8
2024
pubmed:
31
8
2024
entrez:
28
8
2024
Statut:
epublish
Résumé
We have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression. Our bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature. Additionally, PaCSCs exhibited heightened expression of diverse lipid metabolism genes and increased lipid droplet accumulation compared to differentiated progenies. Treatment with palmitic, oleic, and linolenic FAs notably augmented the self-renewal and chemotherapy resistance of CD133 Targeting FAO inhibition represents a promising therapeutic strategy against this highly tumorigenic population.
Sections du résumé
BACKGROUND
BACKGROUND
We have previously demonstrated the significant reliance of pancreatic Cancer Stem Cells (PaCSCs) on mitochondrial oxidative phosphorylation (OXPHOS), which enables versatile substrate utilization, including fatty acids (FAs). Notably, dysregulated lipid scavenging and aberrant FA metabolism are implicated in PDAC progression.
METHODS & RESULTS
RESULTS
Our bioinformatics analyses revealed elevated expression of lipid metabolism-related genes in PDAC tissue samples compared to normal tissue samples, which correlated with a stemness signature. Additionally, PaCSCs exhibited heightened expression of diverse lipid metabolism genes and increased lipid droplet accumulation compared to differentiated progenies. Treatment with palmitic, oleic, and linolenic FAs notably augmented the self-renewal and chemotherapy resistance of CD133
CONCLUSION
CONCLUSIONS
Targeting FAO inhibition represents a promising therapeutic strategy against this highly tumorigenic population.
Identifiants
pubmed: 39198858
doi: 10.1186/s12967-024-05598-6
pii: 10.1186/s12967-024-05598-6
doi:
Substances chimiques
Fatty Acids
0
AC133 Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
797Subventions
Organisme : Worldwide Cancer Research
ID : 19-250
Pays : United Kingdom
Organisme : Instituto de Salud Carlos III
ID : CP16/00121
Organisme : Instituto de Salud Carlos III
ID : CPII21/00005
Organisme : Instituto de Salud Carlos III
ID : FI21/00031
Organisme : Instituto de Salud Carlos III
ID : PI17/00082
Organisme : Instituto de Salud Carlos III
ID : PI20/00921
Organisme : Fundación Científica Asociación Española Contra el Cáncer
ID : LABAE223389SANC
Organisme : Fundación Científica Asociación Española Contra el Cáncer
ID : PRDAR222458ROYO
Organisme : Ministerio de Universidades
ID : CA1/RSUE/202100646
Organisme : Departamento de Educación, Cultura y Deporte, Gobierno de Aragón
ID : Departamento de Educación, Cultura y Deporte, Gobierno de Aragón
Informations de copyright
© 2024. The Author(s).
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