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Lithium chloride inhibits the migration and invasion of osteosarcoma cells by blocking nuclear translocation of phospho-Erk

Authors
 Ju Yeong Kim  ;  Hun Hee Park  ;  Tai-Soon Yong  ;  Soung-Hoo Jeon 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.581 : 74-80, 2021-12 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2021-12
MeSH
Bone Marrow Cells / cytology ; Bone Marrow Cells / drug effects ; Bone Marrow Cells / metabolism ; Cell Line, Tumor ; Cell Movement / drug effects ; Cell Movement / genetics ; Cell Nucleus / drug effects ; Cell Nucleus / metabolism ; Cell Proliferation / drug effects ; Cell Proliferation / genetics ; Diffusion Chambers, Culture ; Epidermal Growth Factor / pharmacology* ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3 beta / genetics ; Glycogen Synthase Kinase 3 beta / metabolism ; Humans ; Lithium Chloride / pharmacology* ; MAP Kinase Signaling System / drug effects ; Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors ; Mitogen-Activated Protein Kinase 1 / genetics* ; Mitogen-Activated Protein Kinase 1 / metabolism ; Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors ; Mitogen-Activated Protein Kinase 3 / genetics* ; Mitogen-Activated Protein Kinase 3 / metabolism ; Osteoblasts / drug effects* ; Osteoblasts / metabolism ; Osteoblasts / pathology ; Phosphorylation / drug effects ; Primary Cell Culture ; Protein Transport / drug effects ; Wnt Signaling Pathway / drug effects ; beta Catenin / genetics ; beta Catenin / metabolism
Keywords
Epidermal growth factor ; Invasion ; Lithium chloride ; Osteosarcoma ; Proliferation
Abstract
Lithium chloride (LiCl) is an important mood-stabilizing therapeutic agent for bipolar disorders, which has also been shown to inhibit cancer cell metastasis. Investigations of LiCl-induced signaling have focused mainly on extracellular signal regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3 (GSK-3). However, little is known about the differences in cellular activities resulting from specific signaling via each of these pathways. In this study, we investigated the difference in responses between the Wnt/β-catenin and ERK pathways by LiCl or epidermal growth factor (EGF) treatment of osteosarcoma cells. In particular, we analyzed the mechanisms responsible for differences in cell mobility and cell proliferation when pERK or β-catenin is activated. In osteosarcoma cells treated with LiCl or EGF, active β-catenin and p-ERK protein levels were significantly increased compared to those in the control group. However, in wound healing and transwell invasion assays, U2OS and SaOS2 cell migration was significantly reduced by LiCl treatment but increased by EGF treatment. In addition, the proliferation of U2OS cells was reduced by LiCl treatment but increased by EGF treatment. Using immunofluorescence microscopy, we observed nuclear accumulation of phosphorylated ERK (pERK) with EGF treatment, but pERK was restricted to the perinuclear area with LiCl treatment. These results were confirmed using immunoblot assays after subcellular fractionation. Together, these data suggest that LiCl interferes with the translocation of pERK from the cytoplasm to the nucleus.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X21014327
DOI
10.1016/j.bbrc.2021.10.025
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ju Young(김주영) ORCID logo https://orcid.org/0000-0003-2456-6298
Yong, Tai Soon(용태순) ORCID logo https://orcid.org/0000-0002-3445-0769
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190626
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