FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters
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- Li, Mengjiao
- Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University
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- 西村, 建徳
- Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University
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- 竹内, 康人
- Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University; Institute for Frontier Science Initiative, Kanazawa University
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- 本宮, 綱記
- Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University
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- Wang, Yuming
- Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University
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- 塩川, 大介
- Division of Cancer Differentiation, National Cancer Center Research Institute
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- Wang, Kang
- Department of Oncology-Pathology, Karolinska Institute, Karolinska University Hospital
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- 廣瀬, 遥香
- Division of Systems Biology, Graduate School of Medicine, Nagoya University
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- 笹原, 麻子
- Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo
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- 矢野, 正雄
- Department of Surgery, Minami-machida Hospital
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- 石川, 聡子
- Department of Breast Oncology, Kanazawa University Hospital
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- 井口, 雅史
- Department of Breast Oncology, Kanazawa University Hospital
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- 太田, 哲生
- Department of Breast Oncology, Kanazawa University Hospital
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- 田辺, 真彦
- Department of Breast and Endocrine Surgery, Graduate School of Medicine, The University of Tokyo
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- 多田, 敬一郎
- Department of Breast and Endocrine Surgery, Nihon University
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- 秋山, 徹
- Laboratory of Molecular and Genetic Information, Institute for Quantitative Biosciences, The University of Tokyo
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- Cheng, Xi
- Department of Oncology, Shanghai Medical College, Fudan University
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- Liu, Chia-Chi
- North Shore Heart Research Group, Kolling Institute, University of Sydney
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- 山下, 年成
- Department of Breast and Endocrine Surgery, Kanagawa Cancer Center
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- 菅野, 純夫
- Tokyo Medical and Dental University
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- 内田, 雄太郎
- Department of Systems Biomedicine, Tokyo Medical and Dental University
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- 千葉, 朋希
- Department of Systems Biomedicine, Tokyo Medical and Dental University
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- 浅原, 弘嗣
- Department of Systems Biomedicine, Tokyo Medical and Dental University
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- 中川, 正宏
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University
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- 佐藤, 慎哉
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute
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- 宮城, 洋平
- Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute
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- 島村, 徹平
- Division of Systems Biology, Graduate School of Medicine, Nagoya University
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- Nagai, Luis Augusto E.
- Laboratory of Computational Genomics, Institute for Quantitative Biosciences, The University of Tokyo
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- 金井, 昭教
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Biosciences, The University of Tokyo
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- 加藤, 愛巳
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo; Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo
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- 野村, 征太郎
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo; Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo; Department of Frontier Cardiovascular Science, Graduate School of Medicine, The University of Tokyo
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- 中戸, 隆一郎
- Laboratory of Computational Genomics, Institute for Quantitative Biosciences, The University of Tokyo
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- 鈴木, 穣
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Biosciences, The University of Tokyo
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- 東條, 有伸
- Tokyo Medical and Dental University; Institute of Medical Science, The University of Tokyo
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- Voon, Dominic C.
- Institute for Frontier Science Initiative, Kanazawa University; Inflammation and Epithelial Plasticity Unit, Cancer Research Institute, Kanazawa University
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- 小川, 誠司
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University
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- 岡本, 康司
- Division of Cancer Differentiation, National Cancer Center Research Institute; Advanced Comprehensive Research Organization, Teikyo University
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- Foukakis, Theodoros
- Department of Oncology-Pathology, Karolinska Institute, Karolinska University Hospital
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- 後藤, 典子
- Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University; Institute for Frontier Science Initiative, Kanazawa University
説明
The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.
収録刊行物
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- Journal of Clinical Investigation
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Journal of Clinical Investigation 133 (22), 2023-11-15
American Society for Clinical Investigation
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キーワード
詳細情報 詳細情報について
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- CRID
- 1050016726134252160
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- ISSN
- 15588238
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- HANDLE
- 2433/286114
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- PubMed
- 37966117
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
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