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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.

Type Journal
ISBN 2211-1247 (Electronic)
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 Dr David Gallego-Ortega
Publisher Name Cell Reports
Published Date 2021-04-30
Published Volume 35
Published Issue 2
Published Pages 108945
Status Published in-print
DOI 10.1016/j.celrep.2021.108945
URL link to publisher's version