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Mapping the transcriptional evolution of human metastatic breast cancer
Melissa Q. Reeves
Melissa Q. Reeves
Published September 3, 2024
Citation Information: J Clin Invest. 2024;134(17):e183971. https://doi.org/10.1172/JCI183971.
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Commentary

Mapping the transcriptional evolution of human metastatic breast cancer

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Abstract

Many aspects of breast cancer metastasis remain poorly understood, despite its clinical importance. In this issue of the JCI, Winkler et al. have applied an elegant patient-derived xenograft (PDX) model to map the transcriptomes of single cells in matched primary tumors and lung metastases across 13 breast cancer PDX models. They identified distinct transcriptional changes associated with metastatic evolution in lowly and highly metastatic primary tumors. Furthermore, by classifying the “epithelial-mesenchymal plasticity” (EMP) state of single cells, they revealed that considerable EMP heterogeneity exists among primary and metastatic human breast cancer cells. However, the EMP profile of a tumor does not change substantially upon metastasis. These findings give an unprecedentedly detailed view into the transcriptional heterogeneity and evolution of metastatic human breast cancer.

Authors

Melissa Q. Reeves

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Figure 1

Transcriptional heterogeneity and evolution of metastatic breast cancer.

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Transcriptional heterogeneity and evolution of metastatic breast cancer....
Human breast cancer cells exhibit substantial intratumoral heterogeneity of EMP states. Within a given breast cancer subtype, more highly metastatic primary tumors are more likely to contain a larger proportion of mesenchymal-like cells compared with lowly metastatic tumors. Upon metastasis to the lung, the EMP profile of the primary tumor is retained. Transcriptional evolution during metastasis, instead of involving changes in the EMP profile, is characterized by upregulation of stress response genes in highly metastatic primary tumors, or of motility genes in lowly metastatic primary tumors.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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