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Inflammation awakens dormant cancer cells by modulating epithelial-mesenchymal phenotypic state

GSE280817 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 20 samples Submitted 2025/08/19 Platform GPL22245Platform GPL24676Platform GPL16791
Summary
The awakening of dormant disseminated cancer cells appears to be responsible for the clinical relapses of patients whose primary tumors have been successfully cured months and even years earlier. In the present study, we demonstrate that dormant breast cancer cells lodged in the lungs reside in a highly mesenchymal, non-proliferative phenotypic state. The awakening of these cells is not triggered by a cancer cell-autonomous process. Instead, lung inflammation induced by the chemotherapeutic agent bleomycin effectively awakens dormant cancer cells, providing useful models for studying metastatic awakening. Mechanistically, the awakened cells shift from a highly mesenchymal to a quasi-mesenchymal phenotypic state in which they acquire tumorigenicity and proliferative ability. Once awakened, these cells can stably reside in this quasi-mesenchymal state and maintain their tumor-initiating ability, doing so without ongoing heterotypic signaling from the lung microenvironment. EGFR ligands released by the cells of the injured tissue microenvironment, including notably M2 type macrophages, promote dormant cancer cells to move toward this quasi-mesenchymal state, a transition that is critical for the awakening process. An understanding of the mechanisms of metastatic awakening may lead in the future to treatment strategies designed to prevent such awakening and resulting metastatic relapse.
Published in
Inflammation awakens dormant cancer cells by modulating the epithelial-mesenchymal phenotypic state
Zhang J, Zhang J, Han L et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 40901881 · doi:10.1073/pnas.2515009122
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Direct links to NCBI, no account and no request form: the whole study as GSE280817_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 20 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1180601 and SRA study SRP506264. Searching any of these in the dataset finder brings you back here.

Study design
5 conditions, mostly in duplicate
Sum159 ITGB4 low clone 1 biol ×3 Sum159 ITGB4 low clone 1 bleomycin treated bi… ×3 Day3 control ×2 Day3 Bleomycin ×2 Sum159 ITGB4 high cells biol ×2 Day7 control ×1 Day7 Bleomycin ×1 Sum159 ITGB4 high cells ×1 +5 more

Supports a case/control comparison: 6 samples read as cases, 5 as controls.

5 replicated groups read from 20 sample titles; they account for 12 of them. Check it against the sample list below before relying on it.

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