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

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. Lobie () and Tao Zhu ()
Additional contact information
Mingming Wu: University of Science and Technology of China
Xiao Zhang: University of Science and Technology of China
Weijie Zhang: University of Science and Technology of China
Yi Shiou Chiou: Tsinghua Shenzhen International Graduate School
Wenchang Qian: University of Science and Technology of China
Xiangtian Liu: University of Science and Technology of China
Min Zhang: 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
Tao Zhu: University of Science and Technology of China

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29018-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29018-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29018-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().