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Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

Kikhtyak Zoya; Roden Daniel Lee; Castillo Lesley; Law Andrew Man Kit; Rodriguez de la Fuente Laura; Timpson Paul; Sikta Neblina; Cox Thomas Robert; O’Donoghue Seán Ignatius; Conway James Ronald William; Papanicolaou Michael; Venhuizen Jeron; Salomon Robert; Murphy Kendelle Joan; Oakes Samantha Richelle; Magenau Astrid; Gallego-Ortega David; Ormandy Christopher John; Farbehi Nona; Colino-Sanguino Yolanda; Gloss Brian Stewart; Valdés-Mora Fátima

Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

Kikhtyak Zoya
Roden Daniel Lee
Castillo Lesley
Law Andrew Man Kit
Rodriguez de la Fuente Laura
Timpson Paul
Sikta Neblina
Cox Thomas Robert
O’Donoghue Seán Ignatius
Conway James Ronald William
Papanicolaou Michael
Venhuizen Jeron
Salomon Robert
Murphy Kendelle Joan
Oakes Samantha Richelle
Magenau Astrid
Gallego-Ortega David
Ormandy Christopher John
Farbehi Nona
Colino-Sanguino Yolanda
Gloss Brian Stewart
Valdés-Mora Fátima
Katso/Avaa
mmc5.pdf (30.02Mb)
Lataukset: 

doi:10.1016/j.celrep.2021.108945
URI
https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00259-X
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe202301122438
Tiivistelmä

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.

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