How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? - A link with altered cellular metabolomics.
Anchorage-independent growth
Anoikis
Anoikis resistance
Metabolomics
Metastasis
Non-small-cell lung cancer
Journal
Biological research
ISSN: 0717-6287
Titre abrégé: Biol Res
Pays: England
ID NLM: 9308271
Informations de publication
Date de publication:
05 Aug 2023
05 Aug 2023
Historique:
received:
12
04
2023
accepted:
14
07
2023
medline:
7
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
epublish
Résumé
Malignant cells adopt anoikis resistance to survive anchorage-free stresses and initiate cancer metastasis. It is still unknown how varying periods of anchorage loss contribute to anoikis resistance, cell migration, and metabolic reprogramming of cancerous cells. Our study demonstrated that prolonging the anchorage-free lifetime of non-small-cell lung cancer NCI-H460 cells for 7 days strengthened anoikis resistance, as shown by higher half-life and capability to survive and grow without anchorage, compared to wild-type cells or those losing anchorage for 3 days. While the prolonged anchorage-free lifetime was responsible for the increased aggressive feature of survival cells to perform rapid 3-dimensional migration during the first 3 h of a transwell assay, no significant influence was observed with 2-dimensional surface migration detected at 12 and 24 h by a wound-healing method. Metabolomics analysis revealed significant alteration in the intracellular levels of six (oxalic acid, cholesterol, 1-ethylpyrrolidine, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, β-alanine, and putrescine) among all 37 identified metabolites during 7 days without anchorage. Based on significance values, enrichment ratios, and impact scores of all metabolites and their associated pathways, three principal metabolic activities (non-standard amino acid metabolism, cell membrane biosynthesis, and oxidative stress response) offered potential links with anoikis resistance. These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
Malignant cells adopt anoikis resistance to survive anchorage-free stresses and initiate cancer metastasis. It is still unknown how varying periods of anchorage loss contribute to anoikis resistance, cell migration, and metabolic reprogramming of cancerous cells.
RESULTS
RESULTS
Our study demonstrated that prolonging the anchorage-free lifetime of non-small-cell lung cancer NCI-H460 cells for 7 days strengthened anoikis resistance, as shown by higher half-life and capability to survive and grow without anchorage, compared to wild-type cells or those losing anchorage for 3 days. While the prolonged anchorage-free lifetime was responsible for the increased aggressive feature of survival cells to perform rapid 3-dimensional migration during the first 3 h of a transwell assay, no significant influence was observed with 2-dimensional surface migration detected at 12 and 24 h by a wound-healing method. Metabolomics analysis revealed significant alteration in the intracellular levels of six (oxalic acid, cholesterol, 1-ethylpyrrolidine, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, β-alanine, and putrescine) among all 37 identified metabolites during 7 days without anchorage. Based on significance values, enrichment ratios, and impact scores of all metabolites and their associated pathways, three principal metabolic activities (non-standard amino acid metabolism, cell membrane biosynthesis, and oxidative stress response) offered potential links with anoikis resistance.
CONCLUSIONS
CONCLUSIONS
These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.
Identifiants
pubmed: 37542350
doi: 10.1186/s40659-023-00456-z
pii: 10.1186/s40659-023-00456-z
pmc: PMC10403914
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
44Subventions
Organisme : Thailand Science Research and Innovation Fund Chulalongkorn University
ID : CU_FRB65_hea (60)_069_33_13
Informations de copyright
© 2023. Sociedad de Biologia de Chile.
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