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Sumoylated Etv1 establishes mouse mammary cancer stem cells that support tumorigenesis by non-stem cancer cells
Journal article   Peer reviewed

Sumoylated Etv1 establishes mouse mammary cancer stem cells that support tumorigenesis by non-stem cancer cells

Zhijie Li, Kelsey E Koch, Dakota T Thompson, Dana M Van der Heide, Jeremy Chang, Christopher M Franke, Mohammed O Suraju, Anna C Beck, Allison W Lorenzen, Jeffrey R White, …
Developmental cell, Vol.60(17), pp.2264-2278.e7
09/2025
DOI: 10.1016/j.devcel.2025.04.005
PMCID: PMC12353075
PMID: 40315856
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC12353075/View
Open Access

Abstract

The small ubiquitin-like modifier (SUMO) pathway is required for maintenance of cancer stem cells/tumor-initiating cells (CSCs/TICs), which drive tumorigenesis when transplanted into immunocompromised mice. We found that inhibition of the SUMO pathway blocked Neu-mediated mammary oncogenesis and inhibited the function of CSCs/TICs without effects on normal mammary stem cells. Transcriptomic analysis implicated SUMO-conjugated Etv1 as being critical for oncogenesis. After SUMO pathway inhibition, a SUMO-mimetic Etv1 protein, created by a fusion with SUMO1 or SUMO2, established a stem-like cell capable of tumorigenesis, whereas a SUMO-resistant Etv1 protein established a proliferative, non-tumorigenic cell. In mixing experiments, stem-like cells induced tumorigenesis by non-stem cells. We conclude that SUMO-conjugated Etv1 is necessary to maintain the CSC/TIC phenotype and that crosstalk between stem and non-stem cells is crucial for tumorigenesis. The findings demonstrate dynamic interactions between heterogeneous cell types to drive tumorigenesis, which has implications for future cancer therapeutic development.
Stem Cells Transcription Breast Cancer sumoylation cancer stem cell mammary oncogenesis mouse mammary carcinoma Etv1 tumorigenesis neu

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