PMID- 32314963
OWN - NLM
STAT- MEDLINE
DCOM- 20210331
LR  - 20210331
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 9
DP  - 2020 Apr 21
TI  - ERK3/MAPK6 controls IL-8 production and chemotaxis.
LID - 10.7554/eLife.52511 [doi]
LID - e52511
AB  - ERK3 is a ubiquitously expressed member of the atypical mitogen activated protein 
      kinases (MAPKs) and the physiological significance of its short half-life remains 
      unclear. By employing gastrointestinal 3D organoids, we detect that ERK3 protein 
      levels steadily decrease during epithelial differentiation. ERK3 is not required 
      for 3D growth of human gastric epithelium. However, ERK3 is stabilized and 
      activated in tumorigenic cells, but deteriorates over time in primary cells in 
      response to lipopolysaccharide (LPS). ERK3 is necessary for production of several 
      cellular factors including interleukin-8 (IL-8), in both, normal and tumorigenic 
      cells. Particularly, ERK3 is critical for AP-1 signaling through its interaction 
      and regulation of c-Jun protein. The secretome of ERK3-deficient cells is 
      defective in chemotaxis of neutrophils and monocytes both in vitro and in vivo. 
      Further, knockdown of ERK3 reduces metastatic potential of invasive breast cancer 
      cells. We unveil an ERK3-mediated regulation of IL-8 and epithelial secretome for 
      chemotaxis.
CI  - (c) 2020, Bogucka et al.
FAU - Bogucka, Katarzyna
AU  - Bogucka K
AD  - Cell Biology Unit, University Medical Center of the Johannes Gutenberg University 
      Mainz, Mainz, Germany.
FAU - Pompaiah, Malvika
AU  - Pompaiah M
AD  - Cell Biology Unit, University Medical Center of the Johannes Gutenberg University 
      Mainz, Mainz, Germany.
FAU - Marini, Federico
AU  - Marini F
AUID- ORCID: 0000-0003-3252-7758
AD  - Institute of Medical Biostatistics, Epidemiology and Informatics, University 
      Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
AD  - Center for Thrombosis and Hemostasis (CTH), University Medical Center of the 
      Johannes Gutenberg University Mainz, Mainz, Germany.
FAU - Binder, Harald
AU  - Binder H
AD  - Institute of Medical Biostatistics, Epidemiology and Informatics, University 
      Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
AD  - Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical 
      Center - University of Freiburg, Freiburg, Germany.
FAU - Harms, Gregory
AU  - Harms G
AD  - Cell Biology Unit, University Medical Center of the Johannes Gutenberg University 
      Mainz, Mainz, Germany.
AD  - Departments of Biology and Physics, Wilkes University, Wilkes Barre, United 
      States.
FAU - Kaulich, Manuel
AU  - Kaulich M
AUID- ORCID: 0000-0002-9528-8822
AD  - Gene Editing Group, Institute of Biochemistry II, Goethe University, Frankfurt, 
      Germany.
AD  - Frankfurt Cancer Institute, Frankfurt, Germany.
FAU - Klein, Matthias
AU  - Klein M
AD  - Institute of Immunology, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Michel, Christian
AU  - Michel C
AD  - Department of Hematology, Medical Oncology, & Pneumology, University Medical 
      Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
FAU - Radsak, Markus P
AU  - Radsak MP
AD  - Department of Hematology, Medical Oncology, & Pneumology, University Medical 
      Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
FAU - Rosigkeit, Sebastian
AU  - Rosigkeit S
AD  - Cell Biology Unit, University Medical Center of the Johannes Gutenberg University 
      Mainz, Mainz, Germany.
FAU - Grimminger, Peter
AU  - Grimminger P
AD  - Department of General, Visceral- and Transplant Surgery, University Medical 
      Center, Mainz, Germany.
FAU - Schild, Hansjorg
AU  - Schild H
AD  - Institute of Immunology, University Medical Center of the Johannes Gutenberg 
      University Mainz, Mainz, Germany.
FAU - Rajalingam, Krishnaraj
AU  - Rajalingam K
AUID- ORCID: 0000-0002-4175-9633
AD  - Cell Biology Unit, University Medical Center of the Johannes Gutenberg University 
      Mainz, Mainz, Germany.
AD  - University Cancer Center Mainz, University Medical Center Mainz, Mainz, Germany.
LA  - eng
SI  - GEO/GSE136002
GR  - RA1739/4-1/Deutsche Forschungsgemeinschaft/
GR  - CRC1292/Deutsche Forschungsgemeinschaft/
GR  - ERK-KR/Merck KGaA/
GR  - SUNMAPK/Else Kroner-Fresenius-Stiftung/
GR  - RA1739/4-2/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200421
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Interleukin-8)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 6)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chemotaxis, Leukocyte/*physiology
MH  - Gene Expression Regulation/physiology
MH  - Heterografts
MH  - Humans
MH  - Interleukin-8/*metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 6/*metabolism
PMC - PMC7192585
OTO - NOTNLM
OT  - ERK3
OT  - IL-8
OT  - MAPK
OT  - cell biology
OT  - chemotaxis
OT  - gastrointestinal organoids
OT  - human
OT  - metastasis
OT  - mouse
OT  - secretome
OT  - signal transduction
COIS- KB, MP, FM, HB, GH, MK, MK, CM, MR, SR, PG, HS, KR No competing interests 
      declared
EDAT- 2020/04/22 06:00
MHDA- 2021/04/01 06:00
PMCR- 2020/04/21
CRDT- 2020/04/22 06:00
PHST- 2019/10/07 00:00 [received]
PHST- 2020/04/17 00:00 [accepted]
PHST- 2020/04/22 06:00 [pubmed]
PHST- 2021/04/01 06:00 [medline]
PHST- 2020/04/22 06:00 [entrez]
PHST- 2020/04/21 00:00 [pmc-release]
AID - 52511 [pii]
AID - 10.7554/eLife.52511 [doi]
PST - epublish
SO  - Elife. 2020 Apr 21;9:e52511. doi: 10.7554/eLife.52511.