NSCLC Cells Resistance to PI3K/mTOR Inhibitors Is Mediated by Delta-6 Fatty Acid Desaturase (FADS2)
Articolo
Data di Pubblicazione:
2022
Citazione:
NSCLC Cells Resistance to PI3K/mTOR Inhibitors Is Mediated by Delta-6 Fatty Acid Desaturase (FADS2) / M. Colombo, F. Passarelli, P.A. Corsetto, A.M. Rizzo, M. Marabese, G. De Simone, R. Pastorelli, M. Broggini, L. Brunelli, E. Caiola. - In: CELLS. - ISSN 2073-4409. - 11:23(2022), pp. 3719.1-3719.13. [10.3390/cells11233719]
Abstract:
Hyperactivation of the phosphatidylinositol-3-kinase (PI3K) pathway is one of the most
common events in human cancers. Several efforts have been made toward the identification of
selective PI3K pathway inhibitors. However, the success of these molecules has been partially limited
due to unexpected toxicities, the selection of potentially responsive patients, and intrinsic resistance to
treatments. Metabolic alterations are intimately linked to drug resistance; altered metabolic pathways
can help cancer cells adapt to continuous drug exposure and develop resistant phenotypes. Here
we report the metabolic alterations underlying the non-small cell lung cancer (NSCLC) cell lines
resistant to the usual PI3K-mTOR inhibitor BEZ235. In this study, we identified that an increased
unsaturation degree of lipid species is associated with increased plasma membrane fluidity in cells
with the resistant phenotype and that fatty acid desaturase FADS2 mediates the acquisition of
chemoresistance. Therefore, new studies focused on reversing drug resistance based on membrane
lipid modifications should consider the contribution of desaturase activity.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
non-small-cell lung cancer; BEZ235; drug resistance; PI3K/Akt/mTOR pathway; lipid metabolism
Elenco autori:
M. Colombo, F. Passarelli, P.A. Corsetto, A.M. Rizzo, M. Marabese, G. De Simone, R. Pastorelli, M. Broggini, L. Brunelli, E. Caiola
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