Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency.
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Authors
Simundza, Julia
Incassati, Angela
Chandramouli, Anupama
Lin, Ziyan
Khodadadi-Jamayran, Alireza
Publication Date
2022-03-17Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Spina, E., Simundza, J., Incassati, A., Chandramouli, A., Kugler, M. C., Lin, Z., Khodadadi-Jamayran, A., et al. (2022). Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-28937-x
Description
Funder: Will-Rogers and the Stony Wold-Herbert Foundation
Funder: NYC Peter Rowley award C02857
Funder: The Susan G Komen Foundation For The Cure
Abstract
Gpr125 is an orphan G-protein coupled receptor, with homology to cell adhesion and axonal guidance factors, that is implicated in planar polarity and control of cell movements. By lineage tracing we demonstrate that Gpr125 is a highly specific marker of bipotent mammary stem cells in the embryo and of multiple long-lived unipotent basal mammary progenitors in perinatal and postnatal glands. Nipple-proximal Gpr125+ cells express a transcriptomic profile indicative of chemo-repulsion and cell movement, whereas Gpr125+ cells concentrated at invasive ductal tips display a hybrid epithelial-mesenchymal phenotype and are equipped to bind chemokine and growth factors and secrete a promigratory matrix. Gpr125 progenitors acquire bipotency in the context of transplantation and cancer and are greatly expanded and massed at the pushing margins of short latency MMTV-Wnt1 tumors. High Gpr125 expression identifies patients with particularly poor outcome within the basal breast cancer subtype highlighting its potential utility as a factor to stratify risk.
Keywords
Mammary Glands, Animal, Stem Cells, Animals, Humans, Breast Neoplasms, Mammary Neoplasms, Experimental, Cell Movement, Female
Sponsorship
NHLBI NIH HHS (R56 HL151700)
NIH HHS (S10 OD021747)
NCI NIH HHS (T32 CA009161, P30 CA016087, R21 CA129905)
U.S. Department of Health & (T32GM066704)
U.S. Department of Defense (United States Department of Defense) (W81XWH-17-1-0013 BC160959)
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) (R56-HL151700)
U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) (T32CA009161-44, NIH-R21-CA129905)
U.S. Department of Health & (T32CA009161-44, NIH-R21-CA129905)
U.S. Department of Health & (R56-HL151700)
NIGMS NIH HHS (T32 GM066704)
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) (T32GM066704)
U.S. Department of Defense (W81XWH-17-1-0013 BC160959)
Identifiers
35302059, PMC8931046
External DOI: https://doi.org/10.1038/s41467-022-28937-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336181
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