PMID- 31004257
OWN - NLM
STAT- MEDLINE
DCOM- 20191209
LR  - 20191217
IS  - 1976-3786 (Electronic)
IS  - 0253-6269 (Linking)
VI  - 42
IP  - 6
DP  - 2019 Jun
TI  - The YB-1/EZH2/amphiregulin signaling axis mediates LPA-induced breast cancer cell 
      invasion.
PG  - 519-530
LID - 10.1007/s12272-019-01149-6 [doi]
AB  - Lysophosphatidic acid (LPA) has been known to induce epithelial-mesenchymal 
      transition (EMT) to stimulate cancer cell invasion, and resveratrol 
      (3,5,4'-trans-trihydroxystilbene; REV) suppresses the invasion and metastasis of 
      various cancers. The current study aimed to identify the underlying mechanism by 
      which LPA aggravates breast cancer cell invasion and the reversal of this 
      phenomenon. Immunoblotting and quantitative RT-PCR analysis revealed that LPA 
      induces amphiregulin (AREG) expression. Silencing of Y-box binding protein 1 
      (YB-1) or enhancer of zeste homolog 2 (EZH2) expression efficiently inhibited 
      LPA-induced AREG expression. In addition, transfection of the cells with YB-1 
      siRNA abrogated LPA-induced EZH2 and AREG expression, leading to attenuation of 
      breast cancer cell invasion. Furthermore, we observed that both REV and 
      5-fluorouracil (5-Fu) significantly reduce LPA-induced YB-1 phosphorylation and 
      subsequent breast cancer invasion. Importantly, combined treatment of REV with 
      5-Fu showed more significant inhibition of LPA-induced breast cancer invasion 
      compared to single treatment. Therefore, our data demonstrate that the YB-1/EZH2 
      signaling axis mediates LPA-induced AREG expression and breast cancer cell 
      invasion and its inhibition by REV and 5-Fu, providing potential therapeutic 
      targets and inhibition of breast cancer.
FAU - Cho, Kyung Hwa
AU  - Cho KH
AD  - Department of Pharmacology, College of Medicine, Konyang University, Myunggok 
      Medical Building, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea.
FAU - Jeong, Bo Young
AU  - Jeong BY
AD  - Department of Pharmacology, College of Medicine, Konyang University, Myunggok 
      Medical Building, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea.
FAU - Park, Chang Gyo
AU  - Park CG
AD  - Department of Pharmacology, College of Medicine, Konyang University, Myunggok 
      Medical Building, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea. 
      aruso@konyang.ac.kr.
FAU - Lee, Hoi Young
AU  - Lee HY
AUID- ORCID: 0000-0003-1954-7981
AD  - Department of Pharmacology, College of Medicine, Konyang University, Myunggok 
      Medical Building, 158 Gwanjeodong-ro, Seo-gu, Daejeon, 35365, Republic of Korea. 
      hoi@konyang.ac.kr.
LA  - eng
GR  - 2017R1E1A1A01074091/National Research Foundation of Korea/
GR  - 2017R1A2B4007361/National Research Foundation of Korea/
GR  - 2016R1D1A1B04930418/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20190419
PL  - Korea (South)
TA  - Arch Pharm Res
JT  - Archives of pharmacal research
JID - 8000036
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Lysophospholipids)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Y-Box-Binding Protein 1)
RN  - 0 (YBX1 protein, human)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - PG6M3969SG (lysophosphatidic acid)
RN  - Q369O8926L (Resveratrol)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Amphiregulin/metabolism
MH  - Antimetabolites, Antineoplastic/*pharmacology/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology/therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism/pathology
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Drug Screening Assays, Antitumor
MH  - Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors/genetics/metabolism
MH  - Epithelial-Mesenchymal Transition/drug effects
MH  - Female
MH  - Fluorouracil/pharmacology/therapeutic use
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lysophospholipids/*metabolism
MH  - MCF-7 Cells
MH  - Neoplasm Invasiveness/pathology
MH  - Phosphorylation/drug effects
MH  - RNA, Small Interfering/metabolism
MH  - Resveratrol/pharmacology/therapeutic use
MH  - Signal Transduction/*drug effects
MH  - Y-Box-Binding Protein 1/antagonists & inhibitors/genetics/metabolism
OTO - NOTNLM
OT  - Amphiregulin
OT  - Breast cancer
OT  - Invasion
OT  - Lysophosphatidic acid
OT  - Resveratrol
EDAT- 2019/04/21 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/04/21 06:00
PHST- 2019/01/06 00:00 [received]
PHST- 2019/03/25 00:00 [accepted]
PHST- 2019/04/21 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/04/21 06:00 [entrez]
AID - 10.1007/s12272-019-01149-6 [pii]
AID - 10.1007/s12272-019-01149-6 [doi]
PST - ppublish
SO  - Arch Pharm Res. 2019 Jun;42(6):519-530. doi: 10.1007/s12272-019-01149-6. Epub 
      2019 Apr 19.