How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics

Biological Research

Research Article

Hnin Ei Ei Khine¹  Rungroch Sungthong¹  Chatchai Chaotham²  Rossarin Tansawat³  Pithi Chanvorachote⁴  Somruethai Sumkhemthong⁵ 

[1] Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand;Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand;Center of Excellence in Cancer Cell and Molecular Biology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand;Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand;Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand;Center of Excellence in Cancer Cell and Molecular Biology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 10330, Bangkok, Thailand;School of Pharmacy, Eastern Asia University, 12110, Pathum Thani, Thailand;

关键词: Non-small-cell lung cancer;    Anchorage-independent growth;    Anoikis;    Anoikis resistance;    Metastasis;    Metabolomics;   

DOI  :  10.1186/s40659-023-00456-z

 received in 2023-04-12, accepted in 2023-07-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMalignant 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.ResultsOur 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.ConclusionsThese findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.

【 授权许可】

CC BY   
© Sociedad de Biologia de Chile 2023

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