TY - JOUR T1 - Evolution of metastases-associated fibroblasts in the lung microenvironment is driven by stage-specific transcriptional plasticity JF - bioRxiv DO - 10.1101/778936 SP - 778936 AU - Ophir Shani AU - Yael Raz AU - Lea Monteran AU - Or Megides AU - Hila Shacham AU - Noam Cohen AU - Dana Silverbush AU - Oshrat Levi-Galibov AU - Camilla Avivi AU - Roded Sharan AU - Asaf Madi AU - Ruth Scherz-Shouval AU - Iris Barshack AU - Ilan Tsarfaty AU - Neta Erez Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/06/778936.abstract N2 - Mortality from breast cancer is almost exclusively a result of tumor metastasis, and lungs are one of the main metastatic sites. Cancer-associated fibroblasts (CAFs) are prominent players in the microenvironment of breast cancer. However, their role in the metastatic niche is largely unknown. In this study, we profiled the transcriptional co-evolution of lung fibroblasts isolated from transgenic mice at defined stage-specific time points of metastases formation. Employing multiple knowledge-based platforms of data analysis provided powerful insights on functional and temporal regulation of the transcriptome of fibroblasts. We demonstrate that fibroblasts in lung metastases are transcriptionally dynamic and plastic, and reveal stage-specific gene signatures that imply functional tasks, including extracellular matrix remodeling, stress response and shaping the inflammatory microenvironment. Furthermore, we identified Myc as a central regulator of fibroblast rewiring and found that stromal upregulation of Myc transcriptional networks is associated with worse survival in human breast cancer.Competing Interest StatementThe authors have declared no competing interest. ER -