@article{b2347fa725514766a0b38b8a94ce23f8,
title = "ZFP281 drives a mesenchymal-like dormancy program in early disseminated breast cancer cells that prevents metastatic outgrowth in the lung",
abstract = "Increasing evidence shows that cancer cells can disseminate from early evolved primary lesions much earlier than the classical metastasis models predicted. Here, we reveal at a single-cell resolution that mesenchymal-like (M-like) and pluripotency-like programs coordinate dissemination and a long-lived dormancy program of early disseminated cancer cells (DCCs). The transcription factor ZFP281 induces a permissive state for heterogeneous M-like transcriptional programs, which associate with a dormancy signature and phenotype in vivo. Downregulation of ZFP281 leads to a loss of an invasive, M-like dormancy phenotype and a switch to lung metastatic outgrowth. We also show that FGF2 and TWIST1 induce ZFP281 expression to induce the M-like state, which is linked to CDH1 downregulation and upregulation of CDH11. We found that ZFP281 not only controls the early dissemination of cancer cells but also locks early DCCs in a dormant state by preventing the acquisition of an epithelial-like proliferative program and consequent metastases outgrowth.",
author = "Nobre, {Ana Rita} and Erica Dalla and Jihong Yang and Xin Huang and Lena Wullkopf and Emma Risson and Pedram Razghandi and Anton, {Melisa Lopez} and Wei Zheng and Seoane, {Jose A.} and Christina Curtis and Ephraim Kenigsberg and Jianlong Wang and Aguirre-Ghiso, {Julio A.}",
note = "Funding Information: We thank the Aguirre-Ghiso lab for helpful discussions and thank the expertise and assistance of the Dean{\textquoteright}s Flow Cytometry CoRE and Microscope CoRE, Icahn School of Medicine at Mount Sinai. We thank J.K. Gregory, medical illustrator at Mount Sinai, for the graphical abstract. This work was supported by the National Institutes of Health/National Cancer Institute (CA109182, CA216248, CA218024 and CA196521) and the Samuel Waxman Cancer Research Foundation Tumor Dormancy Program. A.R.N. was funded by the Portuguese Foundation for Science and Technology (SFRH/BD/100380/2014). E.D. was funded by the National Institutes of Health/National Cancer Institute (T32 CA078207). L.W. was funded by the Federal Ministry of Education and Research (DFG project number 431474090). Research in the laboratory of J.W. was supported by grants from NYSTEM (C32569GG and C32583GG) and the National Institutes of Health (R01GM129157, R01HD095938, R01HD097268 and R01HL146664). Funding Information: We thank the Aguirre-Ghiso lab for helpful discussions and thank the expertise and assistance of the Dean{\textquoteright}s Flow Cytometry CoRE and Microscope CoRE, Icahn School of Medicine at Mount Sinai. We thank J.K. Gregory, medical illustrator at Mount Sinai, for the graphical abstract. This work was supported by the National Institutes of Health/National Cancer Institute (CA109182, CA216248, CA218024 and CA196521) and the Samuel Waxman Cancer Research Foundation Tumor Dormancy Program. A.R.N. was funded by the Portuguese Foundation for Science and Technology (SFRH/BD/100380/2014). E.D. was funded by the National Institutes of Health/National Cancer Institute (T32 CA078207). L.W. was funded by the Federal Ministry of Education and Research (DFG project number 431474090). Research in the laboratory of J.W. was supported by grants from NYSTEM (C32569GG and C32583GG) and the National Institutes of Health (R01GM129157, R01HD095938, R01HD097268 and R01HL146664). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = oct,
doi = "10.1038/s43018-022-00424-8",
language = "English",
volume = "3",
pages = "1165--1180",
journal = "Nature Cancer",
issn = "2662-1347",
publisher = "Nature Research",
number = "10",
}