PMID- 23871604
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20220223
IS  - 1875-9777 (Electronic)
IS  - 1934-5909 (Print)
IS  - 1875-9777 (Linking)
VI  - 13
IP  - 3
DP  - 2013 Sep 5
TI  - A role for matrix metalloproteinases in regulating mammary stem cell function via 
      the Wnt signaling pathway.
PG  - 300-13
LID - S1934-5909(13)00263-4 [pii]
LID - 10.1016/j.stem.2013.06.005 [doi]
AB  - The microenvironment provides cues that control the behavior of epithelial stem 
      and progenitor cells. Here, we identify matrix metalloproteinase-3 (MMP3) as a 
      regulator of Wnt signaling and mammary stem cell (MaSC) activity. We show that 
      MMP3 overexpression promotes hyperplastic epithelial growth, surprisingly, in a 
      nonproteolytic manner via its hemopexin (HPX) domain. We demonstrate that 
      MMP3-HPX specifically binds and inactivates Wnt5b, a noncanonical Wnt ligand that 
      inhibits canonical Wnt signaling and mammary epithelial outgrowth in vivo. 
      Indeed, transplants overexpressing MMP3 display increased canonical Wnt 
      signaling, demonstrating that MMP3 is an extracellular regulator of the Wnt 
      signaling pathway. MMP3-deficient mice exhibit decreased MaSC populations and 
      diminished mammary-reconstituting activity, whereas MMP3 overexpression elevates 
      MaSC function, indicating that MMP3 is necessary for the maintenance of MaSCs. 
      Our study reveals a mechanism by a microenvironmental protease that regulates Wnt 
      signaling and impacts adult epithelial stem cell function.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Kessenbrock, Kai
AU  - Kessenbrock K
AD  - Department of Anatomy and Biomedical Sciences Program, University of California, 
      San Francisco, San Francisco, CA 94143, USA.
FAU - Dijkgraaf, Gerrit J P
AU  - Dijkgraaf GJ
FAU - Lawson, Devon A
AU  - Lawson DA
FAU - Littlepage, Laurie E
AU  - Littlepage LE
FAU - Shahi, Payam
AU  - Shahi P
FAU - Pieper, Ursula
AU  - Pieper U
FAU - Werb, Zena
AU  - Werb Z
LA  - eng
GR  - K99 CA181490/CA/NCI NIH HHS/United States
GR  - R00 CA181490/CA/NCI NIH HHS/United States
GR  - R01 CA057621/CA/NCI NIH HHS/United States
GR  - T32 CA108462/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130718
PL  - United States
TA  - Cell Stem Cell
JT  - Cell stem cell
JID - 101311472
RN  - 0 (Repressor Proteins)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt5b protein, mouse)
RN  - 9013-71-2 (Hemopexin)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
CIN - Cell Stem Cell. 2013 Sep 5;13(3):259-60. PMID: 24012364
MH  - Adult Stem Cells/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - Cellular Microenvironment
MH  - Epithelium/*physiology
MH  - Extracellular Matrix/metabolism
MH  - Hemopexin/metabolism
MH  - Mammary Glands, Animal/*cytology
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Protein Binding
MH  - Repressor Proteins/metabolism
MH  - Transgenes/genetics
MH  - Up-Regulation
MH  - Wnt Proteins/genetics/*metabolism
MH  - Wnt Signaling Pathway/genetics
PMC - PMC3769456
MID - NIHMS494573
EDAT- 2013/07/23 06:00
MHDA- 2014/04/09 06:00
PMCR- 2014/09/05
CRDT- 2013/07/23 06:00
PHST- 2012/09/21 00:00 [received]
PHST- 2013/04/03 00:00 [revised]
PHST- 2013/06/07 00:00 [accepted]
PHST- 2013/07/23 06:00 [entrez]
PHST- 2013/07/23 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
PHST- 2014/09/05 00:00 [pmc-release]
AID - S1934-5909(13)00263-4 [pii]
AID - 10.1016/j.stem.2013.06.005 [doi]
PST - ppublish
SO  - Cell Stem Cell. 2013 Sep 5;13(3):300-13. doi: 10.1016/j.stem.2013.06.005. Epub 
      2013 Jul 18.