PMID- 22445895
OWN - NLM
STAT- MEDLINE
DCOM- 20120622
LR  - 20181201
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 420
IP  - 4
DP  - 2012 Apr 20
TI  - Nuclear envelope-localized EGF family protein amphiregulin activates breast 
      cancer cell migration in an EGF-like domain independent manner.
PG  - 721-6
LID - 10.1016/j.bbrc.2012.03.045 [doi]
AB  - Amphiregulin (AREG), an EGF family protein, is synthesized as a type I 
      transmembrane precursor (proAREG) and expressed on the cell surface with an 
      extracellular EGF-like domain and an intracellular short cytoplasmic tail. The 
      ectodomain shedding yields a soluble EGF receptor ligand (soluble AREG) which 
      binds to EGF receptor (EGFR) and concomitantly induces migration of unshed 
      proAREG from the plasma membrane to the nuclear envelope (NE). AREG is known to 
      play a potential role in breast cancer and has been intensively investigated as 
      an EGF receptor ligand, while the function of the NE-localized proAREG remains 
      unknown. In this study we used a truncated mutant that mimics NE-localized 
      proAREG without shedding stimuli to discriminate between the functions of 
      NE-localized and plasma membrane-localized proAREG and demonstrate that 
      NE-localized proAREG activates breast cancer cell migration, but suppresses cell 
      growth. Moreover, the present study shows that induction of cell migration by 
      NE-localized proAREG does not require the extracellular growth factor domain or 
      EGF receptor function. Collectively these data demonstrate a novel function 
      mediated by the intracellular domain of proAREG and suggest a significant role 
      for NE-localized proAREG in driving human breast cancer progression.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Tanaka, Hisae
AU  - Tanaka H
AD  - Osaka University Graduate School of Medicine and Health Science, 1-7 Yamadaoka, 
      Suita, Osaka 565-0871, Japan.
FAU - Nishioka, Yu
AU  - Nishioka Y
FAU - Yokoyama, Yuhki
AU  - Yokoyama Y
FAU - Higashiyama, Shigeki
AU  - Higashiyama S
FAU - Matsuura, Nariaki
AU  - Matsuura N
FAU - Matsuura, Shuji
AU  - Matsuura S
FAU - Hieda, Miki
AU  - Hieda M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120316
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Breast Neoplasms/*metabolism/*pathology
MH  - *Cell Movement
MH  - EGF Family of Proteins
MH  - Epidermal Growth Factor/chemistry/genetics/metabolism
MH  - ErbB Receptors/agonists
MH  - Female
MH  - Glycoproteins/chemistry/genetics/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism
MH  - Nuclear Envelope/*metabolism
MH  - Protein Structure, Tertiary
MH  - Sequence Deletion
EDAT- 2012/03/27 06:00
MHDA- 2012/06/23 06:00
CRDT- 2012/03/27 06:00
PHST- 2012/03/08 00:00 [received]
PHST- 2012/03/09 00:00 [accepted]
PHST- 2012/03/27 06:00 [entrez]
PHST- 2012/03/27 06:00 [pubmed]
PHST- 2012/06/23 06:00 [medline]
AID - S0006-291X(12)00492-5 [pii]
AID - 10.1016/j.bbrc.2012.03.045 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Apr 20;420(4):721-6. doi: 
      10.1016/j.bbrc.2012.03.045. Epub 2012 Mar 16.