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

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Názov: Lithium chloride inhibits the migration and invasion of osteosarcoma cells by blocking nuclear translocation of phospho-Erk
Autori: Ju Yeong Kim, Hun Hee Park, Tai Soon Yong, Soung Hoo Jeon
Prispievatelia: Ju Yeong Kim, Hun Hee Park, Tai-Soon Yong, Soung-Hoo Jeon, Kim, Ju Young
Zdroj: Biochemical and Biophysical Research Communications. 581:74-80
Informácie o vydavateľovi: Elsevier BV, 2021.
Rok vydania: 2021
Predmety: 0301 basic medicine, Osteoblasts / pathology, Culture, Proliferation, Osteoblasts / drug effects, Cell Nucleus / drug effects, MAP Kinase Signaling System / drug effects, Invasion, Cell Movement, beta Catenin / metabolism, Bone Marrow Cells / drug effects, Phosphorylation, Wnt Signaling Pathway, beta Catenin, Bone Marrow Cells / cytology, Mitogen-Activated Protein Kinase 1, Cell Movement / genetics, Diffusion Chambers, Osteosarcoma, 0303 health sciences, Tumor, Mitogen-Activated Protein Kinase 3, Protein Transport / drug effects, Cell Movement / drug effects, Osteoblasts / metabolism, Mitogen-Activated Protein Kinase 3 / genetics, 3. Good health, Gene Expression Regulation, Neoplastic, Protein Transport, Mitogen-Activated Protein Kinase 1 / genetics, Diffusion Chambers, Culture, Cell Proliferation / genetics, beta Catenin / genetics, Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors, MAP Kinase Signaling System, Primary Cell Culture, Epidermal Growth Factor / pharmacology, Bone Marrow Cells, Cell Line, 03 medical and health sciences, Cell Line, Tumor, Glycogen Synthase Kinase 3 beta / genetics, Humans, Cell Proliferation, Cell Nucleus, Neoplastic, Phosphorylation / drug effects, Glycogen Synthase Kinase 3 beta, Osteoblasts, Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors, Epidermal Growth Factor, Cell Nucleus / metabolism, Epidermal growth factor, Bone Marrow Cells / metabolism, Glycogen Synthase Kinase 3 beta / metabolism, Lithium Chloride / pharmacology, Lithium chloride, Gene Expression Regulation, Mitogen-Activated Protein Kinase 1 / metabolism, Wnt Signaling Pathway / drug effects, Cell Proliferation / drug effects, Lithium Chloride, Mitogen-Activated Protein Kinase 3 / metabolism
Popis: 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.
Druh dokumentu: Article
Jazyk: English
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2021.10.025
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/34656851
https://pubmed.ncbi.nlm.nih.gov/34656851/
https://www.sciencedirect.com/science/article/pii/S0006291X21014327
https://www.ncbi.nlm.nih.gov/pubmed/34656851
https://yonsei.pure.elsevier.com/en/publications/lithium-chloride-inhibits-the-migration-and-invasion-of-osteosarc
Rights: Elsevier TDM
CC BY NC ND
Prístupové číslo: edsair.doi.dedup.....1e8beb6e223b593524f8059875b14875
Databáza: OpenAIRE
Popis
Abstrakt: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.
ISSN:0006291X
DOI:10.1016/j.bbrc.2021.10.025