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Noggin contributes to brain metastatic colonization of lung cancer cells
- Title
- Noggin contributes to brain metastatic colonization of lung cancer cells
- Authors
- Lee; Jung Eun; Park; Jihye; Kim; Eun Ju; Ko; Yoon Ho; Hong; Soon Auck; Yang; Seung Ho; Ahn; Young-Ho
- Ewha Authors
- 안영호
- SCOPUS Author ID
- 안영호
- Issue Date
- 2023
- Journal Title
- Cancer Cell International
- ISSN
- 1475-2867
- Citation
- Cancer Cell International vol. 23, no. 1
- Keywords
- Brain metastasis; Lung cancer; Mesenchymal–epithelial transition; Noggin
- Publisher
- BioMed Central Ltd
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Background: Brain metastasis is a common complication among patients with lung cancer, yet the underlying mechanisms remain unclear. In this study, we aimed to investigate the pathogenesis of brain metastasis in lung cancer. Methods: We established highly colonizing metastatic lung cancer cells, A549-M2, through multiple implantations of A549 human lung cancer cells in the carotid artery of athymic nude mice. Results: Compared to parental cells (M0), M2 cells demonstrated slower growth in culture plates and soft agar, as well as lower motility and higher adhesion, key characteristics of mesenchymal–epithelial transition (MET). Further analysis revealed that M2 cells exhibited decreased expression of epithelial–mesenchymal transition markers, including ZEB1 and Vimentin. M2 cells also demonstrated reduced invasiveness in co-culture systems. RNA sequencing and gene set enrichment analysis confirmed that M2 cells underwent MET. Intriguingly, depletion of Noggin, a BMP antagonist, was observed in M2 cells, and replenishment of Noggin restored suppressed migration and invasion of M2 cells. In addition, Noggin knockdown in control M0 cells promoted cell attachment and suppressed cell migration, suggesting that Noggin reduction during brain colonization causes inhibition of migration and invasion of metastatic lung cancer cells. Conclusions: Our results suggest that lung cancer cells undergo MET and lose their motility and invasiveness during brain metastatic colonization, which is dependent on Noggin. © 2023, The Author(s).
- DOI
- 10.1186/s12935-023-03155-7
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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