Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype
Basal breast cancer is associated with younger age, early relapse, and a high mortality rate. Here, we use unbiased droplet-based single-cell RNA sequencing (RNA-seq) to elucidate the cellular basis of tumor progression during the specification of the basal breast cancer subtype from the luminal progenitor population in the MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mammary tumor model. We find that basal-like cancer cells resemble the alveolar lineage that is specified upon pregnancy and encompass the acquisition of an aberrant post-lactation developmental program of involution that triggers remodeling of the tumor microenvironment and metastatic dissemination. This involution mimicry is characterized by a highly interactive multicellular network, with involution cancer-associated fibroblasts playing a pivotal role in extracellular matrix remodeling and immunosuppression. Our results may partially explain the increased risk and poor prognosis of breast cancer associated with childbirth.
|Authors||Valdes-Mora, F.; Salomon, R.; Gloss, B. S.; Law, A. M. K.; Venhuizen, J.; Castillo, L.; Murphy, K. J.; Magenau, A.; Papanicolaou, M.; Rodriguez de la Fuente, L.; Roden, D. L.; Colino-Sanguino, Y.; Kikhtyak, Z.; Farbehi, N.; Conway, J. R. W.; Sikta, N.; Oakes, S. R.; Cox, T. R.; O'Donoghue, S. I.; Timpson, P.; Ormandy, C. J.; Gallego-Ortega, D.|
|Responsible Garvan Author|
|Publisher Name||Cell Reports|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/33852842|