PMID- 24036211
OWN - NLM
STAT- MEDLINE
DCOM- 20140625
LR  - 20211021
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 26
IP  - 1
DP  - 2014 Jan
TI  - HER2/HER3 regulates extracellular acidification and cell migration through MTK1 
      (MEKK4).
PG  - 70-82
LID - S0898-6568(13)00283-0 [pii]
LID - 10.1016/j.cellsig.2013.08.043 [doi]
AB  - Human MAP3K4 (MTK1) functions upstream of mitogen activated protein kinases 
      (MAPKs). In this study we show MTK1 is required for human epidermal growth factor 
      receptor 2/3 (HER2/HER3)-heregulin beta1 (HRG) induced cell migration in MCF-7 
      breast cancer cells. We demonstrate that HRG stimulation leads to association of 
      MTK1 with activated HER3 in MCF-7 and T-47D breast cancer cells. Activated HER3 
      association with MTK1 is dependent on HER2 activation and is decreased by 
      pre-treatment with the HER2 inhibitor, lapatinib. Moreover, we also identify the 
      actin interacting region (AIR) on MTK1. Disruption of actin cytoskeletal 
      polymerization with cytochalasin D inhibited HRG induced MTK1/HER3 association. 
      Additionally, HRG stimulation leads to extracellular acidification that is 
      independent of cellular proliferation. HRG induced extracellular acidification is 
      significantly inhibited when MTK1 is knocked down in MCF-7 cells. Similarly, 
      pre-treatment with lapatinib significantly decreased HRG induced extracellular 
      acidification. Extracellular acidification is linked with cancer cell migration. 
      We performed scratch assays that show HRG induced cell migration in MCF-7 cells. 
      Knockdown of MTK1 significantly inhibited HRG induced cell migration. 
      Furthermore, pre-treatment with lapatinib also significantly decreased cell 
      migration. Cell migration is required for cancer cell metastasis, which is the 
      major cause of cancer patient mortality. We identify MTK1 in the HER2/HER3-HRG 
      mediated extracellular acidification and cell migration pathway in breast cancer 
      cells.
CI  - (c) 2013 Elsevier Inc. All rights reserved.
FAU - Sollome, James J
AU  - Sollome JJ
AD  - The Department of Pharmacology and Toxicology, College of Pharmacy, University of 
      Arizona, Tucson, AZ 85721, USA.
FAU - Thavathiru, Elangovan
AU  - Thavathiru E
FAU - Camenisch, Todd D
AU  - Camenisch TD
FAU - Vaillancourt, Richard R
AU  - Vaillancourt RR
LA  - eng
GR  - R01 ES012007/ES/NIEHS NIH HHS/United States
GR  - T32 ES007091/ES/NIEHS NIH HHS/United States
GR  - P30 ES006694/ES/NIEHS NIH HHS/United States
GR  - ES012007/ES/NIEHS NIH HHS/United States
GR  - ES04940/ES/NIEHS NIH HHS/United States
GR  - ES006694/ES/NIEHS NIH HHS/United States
GR  - P42 ES004940/ES/NIEHS NIH HHS/United States
GR  - ES007091/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130912
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Acids)
RN  - 0 (Actins)
RN  - 0 (Neuregulin-1)
RN  - 155646-83-6 (heregulin beta1)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ERBB3 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.10.1 (Receptor, ErbB-3)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 4)
RN  - EC 2.7.11.25 (MAP3K4 protein, human)
SB  - IM
MH  - Acids/*metabolism
MH  - Actin Cytoskeleton/drug effects/metabolism
MH  - Actins/metabolism
MH  - Amino Acid Sequence
MH  - *Cell Movement/drug effects
MH  - Extracellular Space/drug effects/*metabolism
MH  - Female
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Immunoprecipitation
MH  - MAP Kinase Kinase Kinase 4/chemistry/metabolism
MH  - MCF-7 Cells
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Neuregulin-1/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Phosphotyrosine/metabolism
MH  - Protein Binding/drug effects
MH  - Protein Structure, Tertiary
MH  - Receptor, ErbB-2/*metabolism
MH  - Receptor, ErbB-3/*metabolism
PMC - PMC3869707
MID - NIHMS524981
OTO - NOTNLM
OT  - AIR
OT  - EGF
OT  - EGFR
OT  - ERK
OT  - HER
OT  - HER2
OT  - HER3
OT  - HRG
OT  - LC-MS/MS
OT  - MAP3K4
OT  - MAPK
OT  - MEKK4
OT  - MTK1
OT  - Migration
OT  - Ssk2
OT  - actin interacting region
OT  - cyto D
OT  - cytochalasin D
OT  - epidermal growth factor
OT  - epidermal growth factor receptor
OT  - extracellular signal-regulated kinase
OT  - f-actin
OT  - filamentous actin
OT  - g-actin
OT  - globular actin
OT  - heregulin
OT  - human epidermal growth factor receptor
OT  - liquid chromatography and tandem mass spectrometry
OT  - mitogen activated protein three kinase
OT  - mitogen-activated protein kinase
OT  - mitogen-activated protein kinase kinase kinase 4
OT  - mitogen-activated, extracellular signal-regulated kinase kinase
OT  - pTyr
OT  - phosphotyrosines
OT  - suppressor of sensor kinase
EDAT- 2013/09/17 06:00
MHDA- 2014/06/26 06:00
PMCR- 2015/01/01
CRDT- 2013/09/17 06:00
PHST- 2013/08/23 00:00 [received]
PHST- 2013/08/30 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/06/26 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - S0898-6568(13)00283-0 [pii]
AID - 10.1016/j.cellsig.2013.08.043 [doi]
PST - ppublish
SO  - Cell Signal. 2014 Jan;26(1):70-82. doi: 10.1016/j.cellsig.2013.08.043. Epub 2013 
      Sep 12.