PMID- 32030797
OWN - NLM
STAT- MEDLINE
DCOM- 20210121
LR  - 20210121
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 3
DP  - 2020 Mar
TI  - GPER-regulated lncRNA-Glu promotes glutamate secretion to enhance cellular 
      invasion and metastasis in triple-negative breast cancer.
PG  - 4557-4572
LID - 10.1096/fj.201901384RR [doi]
AB  - Triple-negative breast cancer (TNBC) is a group of breast cancer with 
      heterogeneity and poor prognosis and effective therapeutic targets are not 
      available currently. TNBC has been recognized as estrogen-independent breast 
      cancer, while the novel estrogen receptor, namely G protein-coupled estrogen 
      receptor (GPER), was claimed to mediate estrogenic actions in TNBC tissues and 
      cell lines. Through mRNA microarrays, lncRNA microarrays, and bioinformatics 
      analysis, we found that GPER is activated by 17beta-estradiol (E2) and GPER-specific 
      agonist G1, which downregulates a novel lncRNA (termed as lncRNA-Glu). LncRNA-Glu 
      can inhibit glutamate transport activity and transcriptional activity of its 
      target gene VGLUT2 via specific binding. GPER-mediated reduction of lncRNA-Glu 
      promotes glutamate transport activity and transcriptional activity of VGLUT2. 
      Furthermore, GPER-mediated activation of cAMP-PKA signaling contributes to 
      glutamate secretion. LncRNA-Glu-VGLUT2 signaling synergizes with cAMP-PKA 
      signaling to increase autologous glutamate secretion in TNBC cells, which 
      activates glutamate N-methyl-D-aspartate receptor (NMDAR) and its downstream CaMK 
      and MEK-MAPK pathways, thus enhancing cellular invasion and metastasis in vitro 
      and in vivo. Our data provide new insights into GPER-mediated glutamate secretion 
      and its downstream signaling NMDAR-CaMK/MEK-MAPK during TNBC invasion. The 
      mechanisms we discovered may provide new targets for clinical therapy of TNBC.
CI  - (c) 2020 Federation of American Societies for Experimental Biology.
FAU - Yin, Jiali
AU  - Yin J
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Tu, Gang
AU  - Tu G
AD  - Department of Endocrine and Breast Surgery, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing, China.
FAU - Peng, Meixi
AU  - Peng M
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Zeng, Huan
AU  - Zeng H
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Wan, Xueying
AU  - Wan X
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Qiao, Yina
AU  - Qiao Y
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Qin, Yilu
AU  - Qin Y
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Liu, Manran
AU  - Liu M
AD  - Key Laboratory of Laboratory Medical Diagnostics designated by Chinese Ministry 
      of Education, Chongqing Medical University, Chongqing, China.
FAU - Luo, Haojun
AU  - Luo H
AD  - Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200206
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Vesicular Glutamate Transport Protein 2)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Glutamic Acid/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - Mice
MH  - Mice, Nude
MH  - RNA, Messenger/genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, G-Protein-Coupled/genetics/metabolism
MH  - Signal Transduction/genetics/physiology
MH  - Vesicular Glutamate Transport Protein 2/genetics/*metabolism
OTO - NOTNLM
OT  - G protein-coupled estrogen receptor
OT  - glutamate N-methyl-D-aspartate receptor
OT  - glutamate signaling
OT  - triple-negative breast cancer
EDAT- 2020/02/08 06:00
MHDA- 2021/01/22 06:00
CRDT- 2020/02/08 06:00
PHST- 2019/06/04 00:00 [received]
PHST- 2020/01/07 00:00 [revised]
PHST- 2020/01/17 00:00 [accepted]
PHST- 2020/02/08 06:00 [pubmed]
PHST- 2021/01/22 06:00 [medline]
PHST- 2020/02/08 06:00 [entrez]
AID - 10.1096/fj.201901384RR [doi]
PST - ppublish
SO  - FASEB J. 2020 Mar;34(3):4557-4572. doi: 10.1096/fj.201901384RR. Epub 2020 Feb 6.