5/31/2023 0 Comments Western blot quantificationFurthermore, inhibiting EDI3 leads to a significant reduction in viability and tumor growth, especially in ER- HER2+ breast cancer cells that are resistant to conventional HER2-targeted therapies. Furthermore, inhibition of EDI3 in ER-HER2+ cells resistant to HER2-targeted therapy reduced cell viability in vitro and tumor growth in vivo in mice.īased on these findings, the researchers conclude that EDI3 expression is upregulated in ER-HER2+ breast cancers compared to other subtypes. Inhibition of EDI3, in turn, primarily reduced the viability of ER-HER2+ cells. Silencing of HER2 as well as inhibition of HER2 signaling decreased EDI3 expression. In a recent study published in the Journal of Experimental & Clinical Cancer Research, the researchers showed that EDI3 expression is highest in ER-HER2+ breast tumors in humans and that both expression and enzymatic activity were highest in ER-HER2+ breast cancer cell lines. Targeting EDI3 as a therapeutic approach in ER-HER2+ breast cancer While the importance of choline metabolism in breast cancer has been studied, the role of EDI3 in this type of cancer has not yet been explored. The glycerophosphodiesterase EDI3, which cleaves glycerophosphocholine to choline and glycerol-3-phosphate, influences choline and phospholipid metabolism and has been linked to cancer-relevant functions in vitro. Researchers at IfADo have already identified one such enzyme-EDI3. Enzymes regulate metabolism and are therefore viable candidates for targeted cancer therapies. Tumor cells alter their metabolism in order to maintain growth, thus ensuring their survival. Their most recent results reveal that inhibiting EDI3 may be a new therapeutic target in patients with therapy-resistant ER-HER2+ breast cancer. Researchers at the Leibniz Research Center for Working Environments and Human Factors in Dortmund (IfADo) have already shown that the enzyme EDI3 is associated with changes in the metabolism of cancer cells. Therefore, the identification of new therapies for this patient group is important. Resistance to HER2-targeted therapies can be a problem when treating patients with HER2-positive (HER2+) breast cancer. Credit: Journal of Experimental & Clinical Cancer Research (2023). IHC, immunohistochemistry TMA, tissue microarray NMR, nuclear magnetic resonance. Cell line data (C-F) are mean ± SD of at least three independent experiments. F, Intracellular PCho/GPC ratio measured using NMR spectroscopy. E, EDI3 enzyme activity measured using an enzyme-coupled assay that indirectly measures the release of choline. D, Representative Western blot (left panel) showing pHER2, HER2, EDI3 and ERα protein expression in the panel of breast cancer cell lines, with quantification normalized to β-Actin (right panel). C, qPCR analysis of EDI3 mRNA expression in a panel of breast cancer cell lines of different molecular subtypes normalized to β-Actin. B, EDI3 protein expression in breast cancer subtypes using IHC on a TMA (n = 265) high expression was defined as strong positivity in > 50% of tumor cells, intermediate as weak in >50% or strong in ≤ 50% of tumor cells, and low as negative or weak in ≤ 50% of tumor cells. A, EDI3 (GPCPD1 224826_at) mRNA expression was compared among subtypes defined according to HER2 and ER status in human breast cancer Affymetrix datasets (total n = 540). EDI3 expression and enzyme activity according to HER2 and ER status.
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