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GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells

AIMS: Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory...

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Autores principales: Choi, Ji-Yoon, Lee, Yun Sun, Shim, Da Mi, Lee, Young Keun, Seo, Sung Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The British Editorial Society of Bone & Joint Surgery 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160028/
https://www.ncbi.nlm.nih.gov/pubmed/33993733
http://dx.doi.org/10.1302/2046-3758.105.BJR-2020-0262.R3
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author Choi, Ji-Yoon
Lee, Yun Sun
Shim, Da Mi
Lee, Young Keun
Seo, Sung Wook
author_facet Choi, Ji-Yoon
Lee, Yun Sun
Shim, Da Mi
Lee, Young Keun
Seo, Sung Wook
author_sort Choi, Ji-Yoon
collection PubMed
description AIMS: Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. METHODS: A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. RESULTS: GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. CONCLUSION: The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320.
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spelling pubmed-81600282021-06-04 GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells Choi, Ji-Yoon Lee, Yun Sun Shim, Da Mi Lee, Young Keun Seo, Sung Wook Bone Joint Res Oncology AIMS: Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. METHODS: A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. RESULTS: GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. CONCLUSION: The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320. The British Editorial Society of Bone & Joint Surgery 2021-05-17 /pmc/articles/PMC8160028/ /pubmed/33993733 http://dx.doi.org/10.1302/2046-3758.105.BJR-2020-0262.R3 Text en © 2021 Author(s) et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Oncology
Choi, Ji-Yoon
Lee, Yun Sun
Shim, Da Mi
Lee, Young Keun
Seo, Sung Wook
GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
title GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
title_full GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
title_fullStr GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
title_full_unstemmed GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
title_short GNAQ knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
title_sort gnaq knockdown promotes bone metastasis through epithelial-mesenchymal transition in lung cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160028/
https://www.ncbi.nlm.nih.gov/pubmed/33993733
http://dx.doi.org/10.1302/2046-3758.105.BJR-2020-0262.R3
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