PMID- 22592159
OWN - NLM
STAT- MEDLINE
DCOM- 20121107
LR  - 20211021
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 132
IP  - 9
DP  - 2012 Sep
TI  - Heparin-binding EGF-like growth factor promotes epithelial-mesenchymal transition 
      in human keratinocytes.
PG  - 2148-57
LID - 10.1038/jid.2012.78 [doi]
AB  - We have shown that autocrine proliferation of human keratinocytes (KCs) is 
      strongly dependent upon amphiregulin (AREG), whereas blockade of heparin-binding 
      EGF-like growth factor (HB-EGF) inhibits KC migration in scratch wound assays. 
      Here we demonstrate that expression of soluble HB-EGF (sHB-EGF) or full-length 
      transmembrane HB-EGF (proHB-EGF), but not proAREG, results in profound increases 
      in KC migration and invasiveness in monolayer culture. Coincident with these 
      changes, HB-EGF significantly decreases mRNA expression of several epithelial 
      markers including keratins 1, 5, 10, and 14 while increasing expression of 
      markers of cellular motility including SNAI1, ZEB1, COX-2, and MMP1. 
      Immunostaining revealed HB-EGF-induced expression of the mesenchymal protein 
      vimentin and decreased expression of E-cadherin, as well as nuclear translocation 
      of beta-catenin. Suggestive of a trade-off between KC motility and proliferation, 
      overexpression of HB-EGF also reduced KC growth by >90%. We also show that HB-EGF 
      is strongly induced in regenerating epidermis after partial-thickness wounding of 
      human skin. Taken together, our data suggest that expression of HB-EGF in human 
      KCs triggers a migratory and invasive phenotype with many features of 
      epithelial-mesenchymal transition (EMT), which may be beneficial in the context 
      of cutaneous wound healing.
FAU - Stoll, Stefan W
AU  - Stoll SW
AD  - Department of Dermatology, University of Michigan Medical Center, Ann Arbor, 
      Michigan 48109-5675, USA. sstoll@umich.edu
FAU - Rittie, Laure
AU  - Rittie L
FAU - Johnson, Jessica L
AU  - Johnson JL
FAU - Elder, James T
AU  - Elder JT
LA  - eng
GR  - K01 AR050462-05/AR/NIAMS NIH HHS/United States
GR  - K01 AR059678-03/AR/NIAMS NIH HHS/United States
GR  - R03 AR049420/AR/NIAMS NIH HHS/United States
GR  - K01 AR059678/AR/NIAMS NIH HHS/United States
GR  - K01 AR050462/AR/NIAMS NIH HHS/United States
GR  - R01 AR 052889/AR/NIAMS NIH HHS/United States
GR  - R01 AR052889/AR/NIAMS NIH HHS/United States
GR  - R01 AR052889-05/AR/NIAMS NIH HHS/United States
GR  - R03 AR049420-03/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120517
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (HBEGF protein, human)
RN  - 0 (Heparin-binding EGF-like Growth Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Vimentin)
RN  - 0 (beta Catenin)
RN  - 68238-35-7 (Keratins)
SB  - IM
CIN - J Invest Dermatol. 2012 Sep;132(9):2129-30. PMID: 22895444
MH  - Amphiregulin
MH  - Cadherins/biosynthesis
MH  - Cell Line
MH  - *Cell Movement/drug effects
MH  - Cell Nucleus/drug effects
MH  - Cell Proliferation
MH  - EGF Family of Proteins
MH  - *Epithelial-Mesenchymal Transition
MH  - Glycoproteins/biosynthesis
MH  - Heparin-binding EGF-like Growth Factor
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis/genetics
MH  - Keratinocytes/pathology/*physiology
MH  - Keratins/biosynthesis
MH  - Protein Transport
MH  - Vimentin/biosynthesis
MH  - Wound Healing
MH  - beta Catenin/biosynthesis
PMC - PMC3423535
MID - NIHMS359035
COIS- CONFLICT OF INTEREST: The authors state no conflict of interest.
EDAT- 2012/05/18 06:00
MHDA- 2012/11/08 06:00
PMCR- 2013/03/01
CRDT- 2012/05/18 06:00
PHST- 2012/05/18 06:00 [entrez]
PHST- 2012/05/18 06:00 [pubmed]
PHST- 2012/11/08 06:00 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - S0022-202X(15)35886-3 [pii]
AID - 10.1038/jid.2012.78 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2012 Sep;132(9):2148-57. doi: 10.1038/jid.2012.78. Epub 2012 
      May 17.