PMID- 31346208
OWN - NLM
STAT- MEDLINE
DCOM- 20201021
LR  - 20210110
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Jul 25
TI  - HER2/HER3 regulates lactate secretion and expression of lactate receptor mRNA 
      through the MAP3K4 associated protein GIT1.
PG  - 10823
LID - 10.1038/s41598-019-46954-7 [doi]
LID - 10823
AB  - One of the major features of cancer is Otto Warburg's observation that many 
      tumors have increased extracellular acidification compared to healthy tissues. 
      Since Warburg's observation, the importance of extracellular acidification in 
      cancer is now considered a hallmark of cancer. Human MAP3K4 functions upstream of 
      the p38 and JNK mitogen activated protein kinases (MAPKs). Additionally, MAP3K4 
      is required for cell migration and extracellular acidification of breast cancer 
      cells in response to HER2/HER3 signaling. Here, we demonstrate that GIT1 
      interacts with MAP3K4 by immunoprecipitation, while cellular lactate production 
      and the capacity of MCF-7 cells for anchorage independent growth in soft agar 
      were dependent on GIT1. Additionally, we show that activation of HER2/HER3 
      signaling leads to reduced expression of lactate receptor (GPR81) mRNA and that 
      both, GIT1 and MAP3K4, are necessary for constitutive expression of GPR81 mRNA. 
      Our study suggests that targeting downstream proteins in the HER2/HER3-induced 
      extracellular lactate signaling pathway may be a way to inhibit the Warburg 
      Effect to disrupt tumor growth.
FAU - Garcia-Flores, Alejandro E
AU  - Garcia-Flores AE
AD  - The Department of Pharmacology and Toxicology, College of Pharmacy University of 
      Arizona, Tucson, Arizona, 85721, USA.
FAU - Sollome, James J
AU  - Sollome JJ
AD  - BioAgilytix, Durham, United States.
FAU - Thavathiru, Elangovan
AU  - Thavathiru E
AD  - University of Oklahoma HSC, Oklahoma City, United States.
FAU - Bower, Joseph L
AU  - Bower JL
AUID- ORCID: 0000-0001-5949-2749
AD  - University of Texas Southwestern Medical Center, Dallas, United States.
FAU - Vaillancourt, Richard R
AU  - Vaillancourt RR
AD  - The Department of Pharmacology and Toxicology, College of Pharmacy University of 
      Arizona, Tucson, Arizona, 85721, USA. vaillancourt@pharmacy.arizona.edu.
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  - T34 GM008718/GM/NIGMS NIH HHS/United States
GR  - P42 ES004940/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190725
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (RNA, Messenger)
RN  - 33X04XA5AT (Lactic Acid)
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)
SB  - IM
MH  - Animals
MH  - Cell Movement/physiology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Lactic Acid/*metabolism
MH  - MAP Kinase Kinase Kinase 4/*metabolism
MH  - MCF-7 Cells
MH  - Mice
MH  - Muscle, Skeletal/metabolism
MH  - Phosphorylation
MH  - RNA, Messenger
MH  - Receptor, ErbB-2/*metabolism
MH  - Receptor, ErbB-3/*metabolism
MH  - Signal Transduction/*physiology
MH  - Tumor Microenvironment/*physiology
PMC - PMC6658559
COIS- The authors declare no competing interests.
EDAT- 2019/07/28 06:00
MHDA- 2020/10/22 06:00
PMCR- 2019/07/25
CRDT- 2019/07/27 06:00
PHST- 2019/03/22 00:00 [received]
PHST- 2019/07/03 00:00 [accepted]
PHST- 2019/07/27 06:00 [entrez]
PHST- 2019/07/28 06:00 [pubmed]
PHST- 2020/10/22 06:00 [medline]
PHST- 2019/07/25 00:00 [pmc-release]
AID - 10.1038/s41598-019-46954-7 [pii]
AID - 46954 [pii]
AID - 10.1038/s41598-019-46954-7 [doi]
PST - epublish
SO  - Sci Rep. 2019 Jul 25;9(1):10823. doi: 10.1038/s41598-019-46954-7.