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

Abstract 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 Our stud...

Full description

Bibliographic Details
Main Authors: Rungroch Sungthong, Hnin Ei Ei Khine, Somruethai Sumkhemthong, Pithi Chanvorachote, Rossarin Tansawat, Chatchai Chaotham
Format: Article
Language:English
Published: BMC 2023-08-01
Series:Biological Research
Subjects:
Online Access:https://doi.org/10.1186/s40659-023-00456-z
_version_ 1797578039938252800
author Rungroch Sungthong
Hnin Ei Ei Khine
Somruethai Sumkhemthong
Pithi Chanvorachote
Rossarin Tansawat
Chatchai Chaotham
author_facet Rungroch Sungthong
Hnin Ei Ei Khine
Somruethai Sumkhemthong
Pithi Chanvorachote
Rossarin Tansawat
Chatchai Chaotham
author_sort Rungroch Sungthong
collection DOAJ
description Abstract 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 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 These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.
first_indexed 2024-03-10T22:16:40Z
format Article
id doaj.art-b4c27435e34f4a1b9ba3b7a42a770f56
institution Directory Open Access Journal
issn 0717-6287
language English
last_indexed 2024-03-10T22:16:40Z
publishDate 2023-08-01
publisher BMC
record_format Article
series Biological Research
spelling doaj.art-b4c27435e34f4a1b9ba3b7a42a770f562023-11-19T12:25:44ZengBMCBiological Research0717-62872023-08-0156111210.1186/s40659-023-00456-zHow do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomicsRungroch Sungthong0Hnin Ei Ei Khine1Somruethai Sumkhemthong2Pithi Chanvorachote3Rossarin Tansawat4Chatchai Chaotham5Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityDepartment of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversitySchool of Pharmacy, Eastern Asia UniversityDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityDepartment of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityDepartment of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityAbstract 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 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 These findings further our insights into the evolution of anoikis resistance in lung cancer cells and identify promising biomarkers for early lung cancer diagnosis.https://doi.org/10.1186/s40659-023-00456-zNon-small-cell lung cancerAnchorage-independent growthAnoikisAnoikis resistanceMetastasisMetabolomics
spellingShingle Rungroch Sungthong
Hnin Ei Ei Khine
Somruethai Sumkhemthong
Pithi Chanvorachote
Rossarin Tansawat
Chatchai Chaotham
How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics
Biological Research
Non-small-cell lung cancer
Anchorage-independent growth
Anoikis
Anoikis resistance
Metastasis
Metabolomics
title How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics
title_full How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics
title_fullStr How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics
title_full_unstemmed How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics
title_short How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? – A link with altered cellular metabolomics
title_sort how do prolonged anchorage free lifetimes strengthen non small cell lung cancer cells to evade anoikis a link with altered cellular metabolomics
topic Non-small-cell lung cancer
Anchorage-independent growth
Anoikis
Anoikis resistance
Metastasis
Metabolomics
url https://doi.org/10.1186/s40659-023-00456-z
work_keys_str_mv AT rungrochsungthong howdoprolongedanchoragefreelifetimesstrengthennonsmallcelllungcancercellstoevadeanoikisalinkwithalteredcellularmetabolomics
AT hnineieikhine howdoprolongedanchoragefreelifetimesstrengthennonsmallcelllungcancercellstoevadeanoikisalinkwithalteredcellularmetabolomics
AT somruethaisumkhemthong howdoprolongedanchoragefreelifetimesstrengthennonsmallcelllungcancercellstoevadeanoikisalinkwithalteredcellularmetabolomics
AT pithichanvorachote howdoprolongedanchoragefreelifetimesstrengthennonsmallcelllungcancercellstoevadeanoikisalinkwithalteredcellularmetabolomics
AT rossarintansawat howdoprolongedanchoragefreelifetimesstrengthennonsmallcelllungcancercellstoevadeanoikisalinkwithalteredcellularmetabolomics
AT chatchaichaotham howdoprolongedanchoragefreelifetimesstrengthennonsmallcelllungcancercellstoevadeanoikisalinkwithalteredcellularmetabolomics