| Literature DB >> 33852842 |
Fátima Valdés-Mora1, Robert Salomon2, Brian Stewart Gloss3, Andrew Man Kit Law3, Jeron Venhuizen4, Lesley Castillo4, Kendelle Joan Murphy3, Astrid Magenau4, Michael Papanicolaou5, Laura Rodriguez de la Fuente6, Daniel Lee Roden7, Yolanda Colino-Sanguino8, Zoya Kikhtyak4, Nona Farbehi9, James Ronald William Conway4, Neblina Sikta10, Samantha Richelle Oakes3, Thomas Robert Cox3, Seán Ignatius O'Donoghue11, Paul Timpson3, Christopher John Ormandy3, David Gallego-Ortega12.
Abstract
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.Entities:
Keywords: Elf5; alveolar lineage; basal breast cancer; cancer-associated fibroblast; involution; mammary gland epithelial hierarchy; pregnancy-associated breast cancer; scRNA-seq
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Year: 2021 PMID： 33852842 DOI： 10.1016/j.celrep.2021.108945
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423