Cuproptosis engages in c-Myc-mediated breast cancer stemness

Journal of Translational Medicine

Research

Qin Hu¹  Qin Chen²  Kun Xu²  Runtian Wang²  Xiaoxiang Guan³  Jian Zhang⁴ 

[1] Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, 226001, Nantong, China;Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China;Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, 210029, Nanjing, China;Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, 211166, Nanjing, China;Phase I Clinical Trial Center, Fudan University Shanghai Cancer Center, Shanghai, China;

关键词: Intra-tumoral heterogeneity;    c-Myc;    Cancer stem cell;    Copper-induced cell death;    Cuproptosis;    Tumor microenvironment;   

DOI  :  10.1186/s12967-023-04204-5

 received in 2022-11-15, accepted in 2023-05-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundIntra-tumoral heterogeneity (ITH) is a distinguished hallmark of cancer, and cancer stem cells (CSCs) contribute to this malignant characteristic. Therefore, it is of great significance to investigate and even target the regulatory factors driving intra-tumoral stemness. c-Myc is a vital oncogene frequently overexpressed or amplified in various cancer types, including breast cancer. Our previous study indicated its potential association with breast cancer stem cell (BCSC) biomarkers.MethodsIn this research, we performed immunohistochemical (IHC) staining on sixty breast cancer surgical specimens for c-Myc, CD44, CD24, CD133 and ALDH1A1. Then, we analyzed transcriptomic atlas of 1533 patients with breast cancer from public database.ResultsIHC staining indicated the positive correlation between c-Myc and BCSC phenotype. Then, we used bioinformatic analysis to interrogate transcriptomics data of 1533 breast cancer specimens and identified an intriguing link among c-Myc, cancer stemness and copper-induced cell death (also known as “cuproptosis”). We screened out cuproptosis-related characteristics that predicts poor clinical outcomes and found that the pro-tumoral cuproptosis-based features were putatively enriched in MYC-targets and showed a significantly positive correlation with cancer stemness.ConclusionIn addition to previous reports on its oncogenic roles, c-Myc showed significant correlation to stemness phenotype and copper-induced cell toxicity in breast cancer tissues. Moreover, transcriptomics data demonstrated that pro-tumoral cuproptosis biomarkers had putative positive association with cancer stemness. This research combined clinical samples with large-scale bioinformatic analysis, covered description and deduction, bridged classic oncogenic mechanisms to innovative opportunities, and inspired the development of copper-based nanomaterials in targeting highly heterogeneous tumors.

【 授权许可】

CC BY   
© The Author(s) 2023

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