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...
Main Authors: | , , , , , |
---|---|
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_ | 1827724501353234432 |
---|---|
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 |