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 (mousemammary 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.

Automated summary

The study used unbiased droplet-based single-cell RNA sequencing to elucidate the cellular basis of tumor progression in basal breast cancer, finding that basal-like cancer cells mimic a post-lactation developmental program, leading to remodeling of the tumor microenvironment and metastatic dissemination. This involution mimicry involves a highly interactive multicellular network, with cancer-associated fibroblasts playing a key role in extracellular matrix remodeling and immunosuppression.