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Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis

Author

Listed:
  • Mingming Wu

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Xiao Zhang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Weijie Zhang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Yi Shiou Chiou

    (Tsinghua Shenzhen International Graduate School
    Kaohsiung Medical University
    Shenzhen Bay Laboratory)

  • Wenchang Qian

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Xiangtian Liu

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Min Zhang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Hong Yan

    (University of Science and Technology of China)

  • Shilan Li

    (University of Science and Technology of China)

  • Tao Li

    (The First Affiliated Hospital of Anhui Medical University)

  • Xinghua Han

    (University of Science and Technology of China)

  • Pengxu Qian

    (Zhejiang University School of Medicine, Hangzhou)

  • Suling Liu

    (Fudan University)

  • Yueyin Pan

    (University of Science and Technology of China)

  • Peter E. Lobie

    (Tsinghua Shenzhen International Graduate School
    Shenzhen Bay Laboratory)

  • Tao Zhu

    (University of Science and Technology of China
    University of Science and Technology of China)

Abstract

Cancer cells display phenotypic equilibrium between the stem-like and differentiated states during neoplastic homeostasis. The functional and mechanistic implications of this subpopulation plasticity remain largely unknown. Herein, it is demonstrated that the breast cancer stem cell (BCSC) secretome autonomously compresses the stem cell population. Co-implantation with BCSCs decreases the tumor-initiating capacity yet increases metastasis of accompanying cancer cells, wherein DKK1 is identified as a pivotal factor secreted by BCSCs for such functions. DKK1-promotes differentiation is indispensable for disseminated tumor cell metastatic outgrowth. In contrast, DKK1 inhibitors substantially relieve the metastatic burden by restraining metastatic cells in the dormant state. DKK1 increases the expression of SLC7A11 to protect metastasizing cancer cells from lipid peroxidation and ferroptosis. Combined treatment with a ferroptosis inducer and a DKK1 inhibitor exhibits synergistic effects in diminishing metastasis. Hence, this study deciphers the contribution of CSC-regulated phenotypic plasticity in metastatic colonization and provides therapeutic approaches to limit metastatic outgrowth.

Suggested Citation

  • Mingming Wu & Xiao Zhang & Weijie Zhang & Yi Shiou Chiou & Wenchang Qian & Xiangtian Liu & Min Zhang & Hong Yan & Shilan Li & Tao Li & Xinghua Han & Pengxu Qian & Suling Liu & Yueyin Pan & Peter E. Lo, 2022. "Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29018-9
    DOI: 10.1038/s41467-022-29018-9
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    References listed on IDEAS

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    1. Tannishtha Reya & Hans Clevers, 2005. "Wnt signalling in stem cells and cancer," Nature, Nature, vol. 434(7035), pages 843-850, April.
    2. Ilaria Malanchi & Albert Santamaria-Martínez & Evelyn Susanto & Hong Peng & Hans-Anton Lehr & Jean-Francois Delaloye & Joerg Huelsken, 2012. "Interactions between cancer stem cells and their niche govern metastatic colonization," Nature, Nature, vol. 481(7379), pages 85-89, January.
    3. Vasanthi S. Viswanathan & Matthew J. Ryan & Harshil D. Dhruv & Shubhroz Gill & Ossia M. Eichhoff & Brinton Seashore-Ludlow & Samuel D. Kaffenberger & John K. Eaton & Kenichi Shimada & Andrew J. Aguirr, 2017. "Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway," Nature, Nature, vol. 547(7664), pages 453-457, July.
    4. Weimin Wang & Michael Green & Jae Eun Choi & Miguel Gijón & Paul D. Kennedy & Jeffrey K. Johnson & Peng Liao & Xueting Lang & Ilona Kryczek & Amanda Sell & Houjun Xia & Jiajia Zhou & Gaopeng Li & Jing, 2019. "CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy," Nature, Nature, vol. 569(7755), pages 270-274, May.
    5. Louise van der Weyden & Mark J. Arends & Andrew D. Campbell & Tobias Bald & Hannah Wardle-Jones & Nicola Griggs & Martin Del Castillo Velasco-Herrera & Thomas Tüting & Owen J. Sansom & Natasha A. Karp, 2017. "Genome-wide in vivo screen identifies novel host regulators of metastatic colonization," Nature, Nature, vol. 541(7636), pages 233-236, January.
    6. Naoya Hirata & Shigeru Yamada & Takuji Shoda & Masaaki Kurihara & Yuko Sekino & Yasunari Kanda, 2014. "Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    7. Devon A. Lawson & Nirav R. Bhakta & Kai Kessenbrock & Karin D. Prummel & Ying Yu & Ken Takai & Alicia Zhou & Henok Eyob & Sanjeev Balakrishnan & Chih-Yang Wang & Paul Yaswen & Andrei Goga & Zena Werb, 2015. "Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells," Nature, Nature, vol. 526(7571), pages 131-135, October.
    8. Jessalyn M. Ubellacker & Alpaslan Tasdogan & Vijayashree Ramesh & Bo Shen & Evann C. Mitchell & Misty S. Martin-Sandoval & Zhimin Gu & Michael L. McCormick & Alison B. Durham & Douglas R. Spitz & Zhiy, 2020. "Lymph protects metastasizing melanoma cells from ferroptosis," Nature, Nature, vol. 585(7823), pages 113-118, September.
    9. Samantha W. Alvarez & Vladislav O. Sviderskiy & Erdem M. Terzi & Thales Papagiannakopoulos & Andre L. Moreira & Sylvia Adams & David M. Sabatini & Kıvanç Birsoy & Richard Possemato, 2017. "NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis," Nature, Nature, vol. 551(7682), pages 639-643, November.
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    1. Jiawen Bu & Yixiao Zhang & Sijin Wu & Haonan Li & Lisha Sun & Yang Liu & Xudong Zhu & Xinbo Qiao & Qingtian Ma & Chao Liu & Nan Niu & Jinqi Xue & Guanglei Chen & Yongliang Yang & Caigang Liu, 2023. "KK-LC-1 as a therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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