| Literature DB >> 33878291 |
Weijie Zhang1, Igor L Bado1, Jingyuan Hu2, Ying-Wooi Wan3, Ling Wu1, Hai Wang1, Yang Gao1, Hyun-Hwan Jeong3, Zhan Xu1, Xiaoxin Hao1, Bree M Lege4, Rami Al-Ouran5, Lucian Li5, Jiasong Li6, Liqun Yu1, Swarnima Singh1, Hin Ching Lo1, Muchun Niu7, Jun Liu1, Weiyu Jiang1, Yi Li1, Stephen T C Wong8, Chonghui Cheng4, Zhandong Liu3, Xiang H-F Zhang9.
Abstract
Metastasis has been considered as the terminal step of tumor progression. However, recent genomic studies suggest that many metastases are initiated by further spread of other metastases. Nevertheless, the corresponding pre-clinical models are lacking, and underlying mechanisms are elusive. Using several approaches, including parabiosis and an evolving barcode system, we demonstrated that the bone microenvironment facilitates breast and prostate cancer cells to further metastasize and establish multi-organ secondary metastases. We uncovered that this metastasis-promoting effect is driven by epigenetic reprogramming that confers stem cell-like properties on cancer cells disseminated from bone lesions. Furthermore, we discovered that enhanced EZH2 activity mediates the increased stemness and metastasis capacity. The same findings also apply to single cell-derived populations, indicating mechanisms distinct from clonal selection. Taken together, our work revealed an unappreciated role of the bone microenvironment in metastasis evolution and elucidated an epigenomic reprogramming process driving terminal-stage, multi-organ metastases.Entities:
Keywords: EZH2; bone metastasis; circulating tumor cells; disseminated tumor cells; epigenomic reprograming; evolving barcodes; organ tropism; plasticity; secondary metastasis; stemness
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Year: 2021 PMID： 33878291 PMCID： PMC8087656 DOI： 10.1016/j.cell.2021.03.011
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582