1. Unveiling Alterations of Epigenetic Modifications and Chromatin Architecture Leading to Lipid Metabolic Reprogramming during the Evolutionary Trastuzumab Adaptation of HER2-Positive Breast Cancer.
- Author
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Duan N, Hua Y, Yan X, He Y, Zeng T, Gong J, Fu Z, Li W, and Yin Y
- Subjects
- Humans, Female, Drug Resistance, Neoplasm genetics, Cell Line, Tumor, Antineoplastic Agents, Immunological therapeutic use, Antineoplastic Agents, Immunological pharmacology, Metabolic Reprogramming, Breast Neoplasms genetics, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Trastuzumab therapeutic use, Trastuzumab pharmacology, Epigenesis, Genetic genetics, Epigenesis, Genetic drug effects, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Chromatin metabolism, Chromatin genetics, Lipid Metabolism drug effects, Lipid Metabolism genetics
- Abstract
Secondary trastuzumab resistance represents an evolutionary adaptation of HER2-positive breast cancer during anti-HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their associated genetic and epigenetic mechanisms. Here, transcriptome data is not only characterized but also examined epigenomic and 3D genome architecture information in both trastuzumab-sensitive and secondary-resistant breast cancer cells. The findings reveal that the global metabolic reprogramming associated with trastuzumab resistance may stem from genome-wide alterations in both histone modifications and chromatin structure. Specifically, the transcriptional activities of key genes involved in lipid metabolism appear to be regulated by variant promoter H3K27me3 and H3K4me3 modifications, as well as promoter-enhancer interactions. These discoveries offer valuable insights into how cancer cells adapt to anti-tumor drugs and have the potential to impact future diagnostic and treatment strategies., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
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