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Molecular Atlas of HER2+ Breast Cancer Cells Stimulated with EGF and HRG: Temporal Insights into Mechanisms in Trastuzumab Resistance [ATAC-Seq]

ABSTRACT: Trastuzumab therapy in HER2+ breast cancer patients have mixed success owing to acquired resistance to therapy. In this study, we investigate the cellular mechanisms underlying acquired resistance using -sensitive and -resistant cancer cells (BT474 and BT474R) treated with endogenous ligands EGF and HRG, across time. Our measurements probe early receptor organization through microscopy, signaling events through multi-omic measurements and assess the cellular energetic state through mitochondrial measurements. Our integrative analyses of these multimodal measurements highlight differential mechanisms in both cell lines in response to ligands. In BT474, an active PI3K-AKT-mTORC1 signaling contributes to an active mitochondrial bioenergetic state (glycolysis and lipid metabolism) for both ligands EGF and HRG. A HIF1A mediated increase in cellular bioenergetics is also seen. In BT474R, there is a ligand-dependent activation of signaling cascades. In EGF treated BT474R, an EGFR driven IRF1/STAT1/STAT2 activation with likely impact on cellular bioenergetics is seen, whilst an AR mediated alteration of lipid metabolism is pronounced after HRG treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237605 | GEO | 2024/02/14

REPOSITORIES: GEO

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Molecular Atlas of HER2+ Breast Cancer Cells Stimulated with EGF and HRG: Temporal Insights into Mechanisms in Trastuzumab Resistance [RNA-Seq]

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