1. Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype.
- Author
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Valdés-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., Valdés-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., and Gallego-Ortega, D.
- Abstract
Contains fulltext : 240100.pdf (Publisher’s version ) (Open Access), 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.
- Published
- 2021