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

Valdés-Mora, F; Salomon, R; Gloss, BS; Law, AMK; Venhuizen, J; Castillo, L; Murphy, KJ; Magenau, A; Papanicolaou, M; Rodriguez de la Fuente, L; Roden, DL; Colino-Sanguino, Y; Kikhtyak, Z; Farbehi, N; Conway, JRW; Sikta, N; Oakes, SR; Cox, TR; O'Donoghue, SI; Timpson, P; Ormandy, CJ; Gallego-Ortega, D

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

Valdés-Mora, F Salomon, R

Gloss, BS Law, AMK Venhuizen, J Castillo, L Murphy, KJ Magenau, A Papanicolaou, M Rodriguez de la Fuente, L Roden, DL Colino-Sanguino, Y Kikhtyak, Z Farbehi, N Conway, JRW Sikta, N Oakes, SR Cox, TR O'Donoghue, SI Timpson, P Ormandy, CJ Gallego-Ortega, D

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Publisher:: Elsevier BV
Publication Type:: Journal Article
Citation:: Cell Rep, 2021, 35, (2), pp. 108945
Issue Date:: 2021-04-13

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Field	Value	Language
dc.contributor.author	Valdés-Mora, F
dc.contributor.author	Salomon, R https://orcid.org/0000-0003-4504-2901
dc.contributor.author	Gloss, BS
dc.contributor.author	Law, AMK
dc.contributor.author	Venhuizen, J
dc.contributor.author	Castillo, L
dc.contributor.author	Murphy, KJ
dc.contributor.author	Magenau, A
dc.contributor.author	Papanicolaou, M
dc.contributor.author	Rodriguez de la Fuente, L
dc.contributor.author	Roden, DL
dc.contributor.author	Colino-Sanguino, Y
dc.contributor.author	Kikhtyak, Z
dc.contributor.author	Farbehi, N
dc.contributor.author	Conway, JRW
dc.contributor.author	Sikta, N
dc.contributor.author	Oakes, SR
dc.contributor.author	Cox, TR
dc.contributor.author	O'Donoghue, SI
dc.contributor.author	Timpson, P
dc.contributor.author	Ormandy, CJ
dc.contributor.author	Gallego-Ortega, D
dc.date.accessioned	2021-04-26T00:21:37Z
dc.date.available	2021-03-14
dc.date.available	2021-04-26T00:21:37Z
dc.date.issued	2021-04-13
dc.identifier.citation	Cell Rep, 2021, 35, (2), pp. 108945
dc.identifier.issn	2211-1247
dc.identifier.issn	2211-1247
dc.identifier.uri	http://hdl.handle.net/10453/148348
dc.description.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.
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartof	Cell Rep
dc.relation.isbasedon	10.1016/j.celrep.2021.108945
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.title	Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype.
dc.type	Journal Article
utslib.citation.volume	35
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	open_access	*
dc.date.updated	2021-04-26T00:21:27Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	35
utslib.citation.issue	2

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.

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http://hdl.handle.net/10453/148348