ZFP281 drives a mesenchymal-like dormancy program in early disseminated breast cancer cells that prevents metastatic outgrowth in the lung

Ana Rita Nobre, Erica Dalla, Jihong Yang, Xin Huang, Lena Wullkopf, Emma Risson, Pedram Razghandi, Melisa Lopez Anton, Wei Zheng, Jose A. Seoane, Christina Curtis, Ephraim Kenigsberg, Jianlong Wang, Julio A. Aguirre-Ghiso

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1165-1180
Number of pages16
JournalNature Cancer
Volume3
Issue number10
DOIs
StatePublished - Oct 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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