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Lung adenocarcinoma cell sensitivity to chemotherapies: a spotlight on lipid droplets and SREBF1 gene

To explore the relationship between cancer cell SREBF1 expression, lipid droplets (LDs) formation, and the sensitivity to chemotherapies, we cultured lung adenocarcinoma cells H1299 (with LD) and H1563 (without LD) in a serum-free basal medium (BM) or neutrophil degranulation products containing med...

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Main Authors: Gründing, Anna Ricarda (Author) , Schneider, Marc (Author) , Richtmann, Sarah (Author) , Kriegsmann, Mark (Author) , Winter, Hauke (Author) , Martinez-Delgado, Beatriz (Author) , Varona, Sarai (Author) , Liu, Bin (Author) , DeLuca, David S. (Author) , Held, Julia (Author) , Wrenger, Sabine (Author) , Muley, Thomas (Author) , Meister, Michael (Author) , Welte, Tobias (Author) , Janciauskiene, Sabina (Author)
Format: Article (Journal)
Language:English
Published: 14 September 2022
In: Cancers
Year: 2022, Volume: 14, Issue: 18, Pages: 1-20
ISSN:2072-6694
DOI:10.3390/cancers14184454
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14184454
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/18/4454
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Author Notes:Anna Ricarda Gründing, Marc A. Schneider, Sarah Richtmann, Mark Kriegsmann, Hauke Winter, Beatriz Martinez-Delgado, Sarai Varona, Bin Liu, David S. DeLuca, Julia Held, Sabine Wrenger, Thomas Muley, Michael Meister, Tobias Welte and Sabina Janciauskiene
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Summary:To explore the relationship between cancer cell SREBF1 expression, lipid droplets (LDs) formation, and the sensitivity to chemotherapies, we cultured lung adenocarcinoma cells H1299 (with LD) and H1563 (without LD) in a serum-free basal medium (BM) or neutrophil degranulation products containing medium (NDM), and tested cell responses to cisplatin and etoposide. By using the DESeq2 Bioconductor package, we detected 674 differentially expressed genes (DEGs) associated with NDM/BM differences between two cell lines, many of these genes were associated with the regulation of sterol and cholesterol biosynthesis processes. Specifically, SREBF1 markedly declined in both cell lines cultured in NDM or when treated with chemotherapeutics. Despite the latter, H1563 exhibited LD formation and resistance to etoposide, but not to cisplatin. Although H1299 cells preserved LDs, these cells were similarly sensitive to both drugs. In a cohort of 292 patients with non-small-cell lung cancer, a lower SREBF1 expression in tumors than in adjacent nontumor tissue correlated with overall better survival, specifically in patients with adenocarcinoma at stage I. Our findings imply that a direct correlation between SREBF1 and LD accumulation can be lost due to the changes in cancer cell environment and/or chemotherapy. The role of LDs in lung cancer development and response to therapies remains to be examined in more detail.
Item Description:Gesehen am 28.10.2022
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers14184454

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