Fatty acid oxidation enzyme Δ3, Δ2-enoyl-CoA isomerase 1 (ECI1) drives aggressive tumor phenotype and predicts poor clinical outcome in prostate cancer patients.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
16
04
2021
accepted:
11
03
2022
revised:
14
02
2022
pubmed:
13
4
2022
medline:
18
5
2022
entrez:
12
4
2022
Statut:
ppublish
Résumé
Prostate cancer (PCa) metastases are highly enriched with genomic alterations including a gain at the 16p13.3 locus, recently shown to be associated with disease progression and poor clinical outcome. ECI1, residing at the 16p13.3 gain region, encodes Δ3, Δ2-Enoyl-CoA Delta Isomerase 1 (ECI1), a key mitochondrial fatty acid β-oxidation enzyme. Although deregulated mitochondrial fatty acid β-oxidation is known to drive PCa pathogenesis, the role of ECI1 in PCa is still unknown. We investigated the impacts of ECI1 on PCa phenotype in vitro and in vivo by modulating its expression in cell lines and assessed the clinical implications of its expression in human prostate tissue samples. In vitro, ECI1 overexpression increased PCa cell growth while ECI1 deficiency reduced its growth. ECI1 also enhanced colony formation, cell motility, and maximal mitochondrial respiratory capacity. In vivo, PCa cells stably overexpressing ECI1 injected orthotopically in nude mice formed larger prostate tumors with higher number of metastases. Immunohistochemistry analysis of the human tissue microarray representing 332 radical prostatectomy cases revealed a stronger ECI1 staining in prostate tumors compared to corresponding benign tissues. ECI1 expression varied amongst tumors and was higher in cases with 16p13.3 gain, high Gleason grade, and advanced tumor stage. ECI1 overexpression was a strong independent predictor of biochemical recurrence after adjusting for known clinicopathologic parameters (hazard ratio: 3.65, P < 0.001) or the established CAPRA-S score (hazard ratio: 3.95, P < 0.001). ECI1 overexpression was also associated with significant increased risk of distant metastasis and reduced overall survival. Overall, this study demonstrates the functional capacity of ECI1 in PCa progression and highlights the clinical implication of ECI1 as a potential target for the management of PCa.
Identifiants
pubmed: 35411033
doi: 10.1038/s41388-022-02276-z
pii: 10.1038/s41388-022-02276-z
doi:
Substances chimiques
Fatty Acids
0
Dodecenoyl-CoA Isomerase
EC 5.3.3.8
ECI1 protein, human
EC 5.3.3.8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2798-2810Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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