PMID- 26907789
OWN - NLM
STAT- MEDLINE
DCOM- 20160725
LR  - 20171116
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 283
IP  - 2
DP  - 2016 Jan
TI  - Helicobacter pylori CagA protein induces factors involved in the epithelial to 
      mesenchymal transition (EMT) in infected gastric epithelial cells in an EPIYA- 
      phosphorylation-dependent manner.
PG  - 206-20
LID - 10.1111/febs.13592 [doi]
AB  - As a result of Helicobacter pylori adhesion to gastric epithelial cells, the 
      bacterial effector cytotoxin-associated gene A (CagA) is translocated 
      intracellularly, and after hierarchical tyrosine phosphorylation on multiple 
      EPIYA motifs, de-regulates cellular polarity and contributes to induction of an 
      elongation and scattering phenotype that resembles the epithelial to mesenchymal 
      transition (EMT). Stromelysin-1/matrix metalloproteinase-3 (MMP-3) has been 
      reported to induce a sequence of molecular alterations leading to stable EMT 
      transition and carcinogenesis in epithelial cells. To identify the putative role 
      of CagA protein in MMP-3 induction, we exploited an experimental H. pylori 
      infection system in gastric epithelial cell lines. We utilized isogenic mutants 
      expressing CagA protein with variable numbers of EPIYA and 
      phosphorylation-deficient EPIFA motifs, as well as cagA knockout and 
      translocation-deficient cagE knockout strains. Increased levels of MMP-3 
      transcriptional activation were demonstrated by quantitative real time-PCR for 
      strains with more than two terminal EPIYA phosphorylation motifs in CagA. MMP-3 
      expression in total cell lysates and the corresponding culture supernatants was 
      associated with CagA expression and translocation and was dependent on CagA 
      phosphorylation. A CagA EPIYA phosphorylation-dependent increase in gelatinase 
      and caseinolytic activity was also detected in culture supernatants by 
      zymography. A significant increase in the transcriptional activity of the 
      mesenchymal markers Vimentin, Snail and ZEB1 and the stem cell marker CD44 was 
      observed in the case of CagA containing phosphorylation-functional EPIYA motifs. 
      Our data suggest that CagA protein induces EMT through EPIYA 
      phosphorylation-dependent up-regulation of MMP-3. Moreover, no significant 
      increase in EMT and stem cell markers was observed following infection with H. 
      pylori strains that cannot effectively translocate CagA protein.
CI  - (c) 2015 FEBS.
FAU - Sougleri, Ioanna S
AU  - Sougleri IS
AD  - Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
FAU - Papadakos, Konstantinos S
AU  - Papadakos KS
AD  - Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
FAU - Zadik, Mairi P
AU  - Zadik MP
AD  - Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
FAU - Mavri-Vavagianni, Mary
AU  - Mavri-Vavagianni M
AD  - Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian 
      University of Athens, Greece.
FAU - Mentis, Andreas F
AU  - Mentis AF
AD  - Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
FAU - Sgouras, Dionyssios N
AU  - Sgouras DN
AUID- ORCID: 0000-0003-0975-2607
AD  - Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
LA  - eng
PT  - Editorial
PT  - Research Support, Non-U.S. Gov't
DEP - 20151211
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (PicB protein, Helicobacter pylori)
RN  - 0 (Vimentin)
RN  - 0 (cagA protein, Helicobacter pylori)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigens, Bacterial/genetics/*metabolism
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Epithelial Cells/*metabolism/microbiology
MH  - *Epithelial-Mesenchymal Transition
MH  - Gastric Mucosa/*metabolism/microbiology
MH  - Helicobacter Infections/*metabolism/pathology
MH  - Helicobacter pylori/*pathogenicity
MH  - Host-Pathogen Interactions
MH  - Humans
MH  - Hyaluronan Receptors/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Vimentin/metabolism
OTO - NOTNLM
OT  - CD44
OT  - MMP-9
OT  - ZEB1
OT  - matrix metalloproteinase
OT  - stromelysin-1/MMP-3
EDAT- 2016/02/26 06:00
MHDA- 2016/07/28 06:00
CRDT- 2016/02/25 06:00
PHST- 2015/07/29 00:00 [received]
PHST- 2015/11/04 00:00 [revised]
PHST- 2015/11/06 00:00 [accepted]
PHST- 2016/02/25 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
AID - 10.1111/febs.13592 [doi]
PST - ppublish
SO  - FEBS J. 2016 Jan;283(2):206-20. doi: 10.1111/febs.13592. Epub 2015 Dec 11.