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Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway

SIMPLE SUMMARY: Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invas...

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Autores principales: Lu, Ko-Hsiu, Yang, Jia-Sin, Hsieh, Yi-Hsien, Chu, Hsiao-Ju, Chou, Chia-Hsuan, Lu, Eric Wun-Hao, Lin, Chiao-Wen, Yang, Shun-Fa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268143/
https://www.ncbi.nlm.nih.gov/pubmed/34202288
http://dx.doi.org/10.3390/cancers13133181
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author Lu, Ko-Hsiu
Yang, Jia-Sin
Hsieh, Yi-Hsien
Chu, Hsiao-Ju
Chou, Chia-Hsuan
Lu, Eric Wun-Hao
Lin, Chiao-Wen
Yang, Shun-Fa
author_facet Lu, Ko-Hsiu
Yang, Jia-Sin
Hsieh, Yi-Hsien
Chu, Hsiao-Ju
Chou, Chia-Hsuan
Lu, Eric Wun-Hao
Lin, Chiao-Wen
Yang, Shun-Fa
author_sort Lu, Ko-Hsiu
collection PubMed
description SIMPLE SUMMARY: Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was decreased by LCN2 knockdown. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the mitogen-activated protein kinases/ERK kinase (MEK)–ERK pathway. ABSTRACT: Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK–ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK–ERK pathway.
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spelling pubmed-82681432021-07-10 Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway Lu, Ko-Hsiu Yang, Jia-Sin Hsieh, Yi-Hsien Chu, Hsiao-Ju Chou, Chia-Hsuan Lu, Eric Wun-Hao Lin, Chiao-Wen Yang, Shun-Fa Cancers (Basel) Article SIMPLE SUMMARY: Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was decreased by LCN2 knockdown. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the mitogen-activated protein kinases/ERK kinase (MEK)–ERK pathway. ABSTRACT: Higher neutrophil-derived cytokine lipocalin-2 (LCN2) expression possesses a versatile role in a myriad of cancers, but little is known about the role of LCN2 on osteosarcoma metastasis. In this study, we demonstrated that higher LCN2 inhibited cellular motility, migration, and invasion of osteosarcoma cells. Moreover, using RNA sequencing technology, we found that LCN2 repressed MET gene expression in U2OS cells. Manipulation of LCN2 levels influenced the migratory potential of osteosarcoma cells as cellular migration was enhanced by transfecting with vectors containing a constitutively active LCN2 cDNA and recombinant human LCN2. Moreover, the phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinase (ERK) kinase (MEK) 1/2 and ERK 1/2 was decreased by LCN2 knockdown. Furthermore, the use of ERK inhibitor (U0126) and activator (tBHQ) confirmed that the pharmaceutic inhibition of MEK–ERK augmented the LCN2-mediated MET suppression and migration of U2OS and HOS cells. Conclusively, LCN2 inhibits osteosarcoma cell metastasis by suppressing MET via the MEK–ERK pathway. MDPI 2021-06-25 /pmc/articles/PMC8268143/ /pubmed/34202288 http://dx.doi.org/10.3390/cancers13133181 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Ko-Hsiu
Yang, Jia-Sin
Hsieh, Yi-Hsien
Chu, Hsiao-Ju
Chou, Chia-Hsuan
Lu, Eric Wun-Hao
Lin, Chiao-Wen
Yang, Shun-Fa
Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
title Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
title_full Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
title_fullStr Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
title_full_unstemmed Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
title_short Lipocalin-2 Inhibits Osteosarcoma Cell Metastasis by Suppressing MET Expression via the MEK–ERK Pathway
title_sort lipocalin-2 inhibits osteosarcoma cell metastasis by suppressing met expression via the mek–erk pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268143/
https://www.ncbi.nlm.nih.gov/pubmed/34202288
http://dx.doi.org/10.3390/cancers13133181
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