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Gpr125 is a unifying hallmark of multiple mammary progenitors coupled to tumor latency.

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Simundza, Julia 
Incassati, Angela 
Chandramouli, Anupama 


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.


Funder: Will-Rogers and the Stony Wold-Herbert Foundation

Funder: NYC Peter Rowley award C02857

Funder: The Susan G Komen Foundation For The Cure


Animals, Breast Neoplasms, Cell Movement, Female, Humans, Mammary Glands, Animal, Mammary Neoplasms, Experimental, Stem Cells

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Nat Commun

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Springer Science and Business Media LLC
NHLBI NIH HHS (R56 HL151700)
NIH HHS (S10 OD021747)
NCI NIH HHS (T32 CA009161, P30 CA016087, R21 CA129905)
U.S. Department of Health &amp (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 &amp (T32CA009161-44, NIH-R21-CA129905)
U.S. Department of Health &amp (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)