1. Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype
- Author
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Fátima Valdés-Mora, Robert Salomon, Brian Stewart Gloss, Andrew Man Kit Law, Jeron Venhuizen, Lesley Castillo, Kendelle Joan Murphy, Astrid Magenau, Michael Papanicolaou, Laura Rodriguez de la Fuente, Daniel Lee Roden, Yolanda Colino-Sanguino, Zoya Kikhtyak, Nona Farbehi, James Ronald William Conway, Neblina Sikta, Samantha Richelle Oakes, Thomas Robert Cox, Seán Ignatius O’Donoghue, Paul Timpson, Christopher John Ormandy, and David Gallego-Ortega
- Subjects
scRNA-seq ,basal breast cancer ,alveolar lineage ,cancer-associated fibroblast ,involution ,pregnancy-associated breast cancer ,Biology (General) ,QH301-705.5 - Abstract
Summary: 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
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